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0 and λ is bounded and bounded away from 0. Typically λ is primarily a function of the direction of x rather than its magnitude. Optimally choosing λ is equivalent to optimally choosing Tj0stheim's m (see below). Furthermore, the geometric drift condition can be expressed in terms of the drift of the logarithm of V(Xt) (the log-drift condition). For the following theorems let Λ be the class of all nonnegative measurable functions on W that are bounded and bounded away from 0. Theorem 1 Assume {Xt} is an aperiodic, φ-irreducible T-chain in W such that E (||ΛΊ||7(1 + ||z|| r ) I XQ = x) is bounded for some r > 0. The following are equivalent conditions, each sufficient for {Xt} to be geometrically ergodic.
(i) ί m s u p | M | _ , o o g ( Λ ( ^ ) ) | | ^ J | r I Xo = x) < 1 for some λ e A, r > 0.
(it) l i m s u p H s i i ^ E ( i j p ί | X°
= x
) < l for
some
r>0,n>m>0.
(in) l i m s u P | N K o o E (log (δ + ^ j j ^ l " ) | *o = x) < 0 for some δ > 0, λeΛ. (iv) limsupiiaju^oo E (log {δ + l^\\χ^) m > 0.
Xo = x) < 0 for some
δ>0,n>
NONLINEAR TS STABILITY
159
Proof The equivalences follow from Cline and Pu (1999a, Lena. 4.1, Lem. 4.2) and the sufficiency for geometric ergodicity from condition (10) with test function V(x) = 1 + λ(z)||z|| r . D If the noise terms in a FCAR(p) model do not dominate when the time series is very large then they may be at least partly ignored, as the following theorem suggests. Theorem 2 Assume {Xt} is an aperiodic, φ-irreducible T-chain defined by r (1) and (6) such that αo,...,α p are bounded, sup|j a .|| < M 2?(|c(ei;£)| ) < oo r r for some r > 0 and all M < oo, and lim||x||_>ooi£ (|c(ei;x)| /||α:|| ) = 0. Let a be given by (8) and θ{x) — (a(x),xι,... ,xp-ι)/(l + ||a?||) for x = (xι,..., xp). The following are equivalent conditions, each sufficient for {Xt} to be geometrically ergodic. (i) U m s u P | W K o o £ ( ^
I Xo = x) \\θ(x)\\r < 1 for some r > 0, λ G Λ.
(it) l i m s u p | N K o o E (j[nj=m ||0(-Xj )IΓ \XQ = X)
D
Similar theorems express equivalent conditions for transience of a Markov chain (e.g., Cline and Pu (2001, Thm. 2.2)). Example 6. We refer to conditions (iii,iv) in Theorem 1 and (iii,iv) in Theorem 2 as "log-drift" conditions. A model which illustrates the benefits of using a log-drift condition is the Periodic FCAR(l) model,
where the coefficient function a\(x) is periodic with period r. This is an unusual model but there is a suggestion of periodicity in the coefficient functions fitted by Chen and Tsay (1993a) for the sunspot number data, and it was at the urging of Prof. Chen that we studied the stability of this particular model. At any rate, it is a useful example. With n = m = 1, the condition in Theorem 2(iv) can be reexpressed as limsupE (log(ί + K(ξi)|) ξo = x) < 0 for some δ > 0.
(13)
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(This can also be determined from the 2-step condition with V(x) — 1 + |x|.) The function E (log(£ + |αχ(£i)|) | ξo = %) is close to being periodic in |αi(x)x|. Thus the left-hand side of (13) is only a limsup, not a limit, which has the unfortunate consequence that condition (13) is not sharp. The solution is to choose n = m — 2 instead. Assume a\(x) is continuously differentiate with a derivative that is 0 on a set of measure 0. Then the function E (log(ί + |αi(ξ2)|) I ξo = x) does in fact have a limit and therefore does lead to a sharp condition, namely if
Γ log(|αi(u)|)*ι<0
(14)
JO
then {ξt} is geometrically ergodic and if f£ log(\aι(u)\)du > 0 then {ξt} is transient (Cline and Pu (1999a, Thm. 3.4; 2001, Thm. 3.2)). Note that the skeleton process, xt = ao(xt-ι) + aι{xt-i)zt-i is geometrically stable if and only if sup|αi(α:)| < 1. Therefore, this is an example where stability of the time series does not coincide with stability of its skeleton. For a specific example, suppose a\{x) = c + dcos(x) with \c\ + \d\ > 1, M < |d| < 2. Then the time series is geometrically ergodic but the skeleton is not stable. Although condition (14) does not explicitly refer to the noise distribution, the noise does play a major role in determining the condition by causing the drift to be averaged. Example 7. The directional method, on the other hand, seems to work well with many threshold models of order 1, including ones that employ a delay. Consider, for example, the TAR(l) time series with delay d given by ξt = ao(Xt-ι) + aι(Xt-i)ξt-i + eu
Xt-ι = (ξt-u
>6-d
ao(x) bounded and a\{x) depends only on (sgn(xχ),... ,s x = (xi,..., Xd). There are thus 2d regions i?χ,..., R2d each corresponding to a coefficient: a\j = 01(1), x G Rj. Notice that the thresholds — boundaries of the regions — are the axial hyperplanes. As long as the time series remains large (which is all that is of concern for stability), ξt avoids the thresholds and hence Xt cycles among some subset of the regions. There may be several such subsets possible, depending on the signs of the αij's, and it is the drift of the "worst case" cycle that is critical. Thus the geometric drift condition for stability is exactly (Cline and Pu (1999b, Cor. 2.4))
max
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where the maximum is taken over the possible cycles described above. This corresponds precisely to the geometric stability of the skeleton. The test function for establishing this condition takes the directional form, V(x) = 1 4- A(rr)||a;||r, and the optimal choice for X(x) is constant on each of the 2d regions. 6. The Piggyback Method. To this point we have presented examples studied with what one might call the traditional methods of drift analysis. Not all models yield to this analysis, however, including some surprisingly simple models. In this section we present a new approach, as yet somewhat informal, that employs a much more sophisticated ra-step test function. We call it the piggyback method because it relies on finding a stable Markov chain similar to a process embedded in the one of interest and building a new test function on top of one that works for the known stable chain. We will first present a sketch of the piggyback method and then provide three examples. The sketch, however, is quite rough because in fact the method is applied somewhat differently for each of the examples. (See the papers referenced below.) Indeed, the concept is elegant but its application is messy and as yet we do not know how generally useful it may prove to be. The time series {ξt} is embedded in a Markov chain {Xt} At the same time we consider another Markov chain {Yt} similar to a simpler process embedded in {Xt}> The chain {Yt} is assumed to be geometrically ergodic and, in particular, to satisfy the geometric drift condition with test function V\{y). Its stationary distribution we denote G. If there is a function H(y) which somehow exemplifies (or bounds) the relative change in magnitude of X\ when XQ is large and YQ — y then, intuitively, the stationary value of H(Yt) will measure the geometric drift of {Xt}- Thus, a log-drift condition for geometric stability would be exp ( ίlog(ί + H(y))G(dy)\ < 1 for some δ > 0.
(15)
To obtain a test function that will yield such a condition, we first define
and let y(x) identify the "embedding" of Yt into Xt An integer m is chosen suitably large, a "correction" function c(x) constructed and the ultimate test function is (something like) l/m
V(x)=c(x)[l[E(h(Yj)\Y0 =
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The key point for this paper is that the piggyback method and the resulting condition for ergodicity capture the implicit stochastic behavior of {F t }, not the behavior of a deterministic skeleton of {Xt} or {£*}. Even if such a skeleton can be identified, its stability properties will not coincide with those of {&}. Alternatively, one may think of {Xt} as having a sort of stochastic skeleton which must be analyzed for stability. Example 8. Our first example is a bivariate threshold model (Cline and Pu (1999a, Ex. 3.2; 2001, Ex. 3.2)). Indeed it is the simplest such model that is not just two independent univariate models joined together. Suppose
where ai(xχ) = α ϋ l X l < o + α^lxjXb i = 1?2. Note that the nonlinearity of the second component Xt^ is driven by the univariate TAR(l) process {Xt,ι} The latter is our "embedded" process and is stable when max(αii,αi2,αiiαi2) < 1.
(16)
Let G be its stationary distribution. The function |α2(#i)| plays the role of H(y) so that the resulting (sharp) stability condition is, in addition to (16),
which represents the stationary value of the relative change in magnitude of Xti2 when it is very large. This condition neither implies nor is implied by the stability condition for the corresponding skeleton process: (16) plus
Example 9. The second example (cf. Cline and Pu (1999c)) is the threshold ARMA(l,ςr) model (TARMA) with a delay d:
ξt = oo(Xt-i) + aι(Xt-i)ξt-i
+et + &i(-ϊt-i)et-i + • +
bq(Xt-ι)et-q,
where Xt-ι = {ξt-i,..., ξt-d), «o3 &i, , bq are bounded and aχ{x) is (asymptotically) piecewise constant. We further assume the thresholds are affine which implies the regions on which a\(x) is constant are cones in Md. This is the simplest interesting example of a TARMA process. See also Brockwell, Liu and Tweedie (1992) and Liu and Susko (1992). In the case q > 0, the time series must be embedded in the Markov chain {(Xt,Ut)} where Xt is as above and Ut = ( e t , . . . , e t _ g +i). Threshold ARMA models have not seen a lot of study, perhaps in part because the moving average terms can affect the irreducibility and periodicity
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properties of the chain in complicated ways as yet not well understood. (See, for example, Cline and Pu (1999c)). This by itself is a major role played by the noise but we will pass by it here. Let the regions i?χ,..., Rm be the partition of W such that a\(x) is constant on each region, with a n , . . . , a i m being the corresponding constants. There are basically two types of situations that arise in these models when ξt is very large: cyclical and noncyclical. For the cyclical situation, {Xt} essentially cycles close to certain rays having the form
(Uϊ:lalji,nPiZΪalji,...,l)xu
(17)
if all are in the interior of the conical regions. Noise plays no role in determining the stability in this situation since Xt avoids the thresholds; all that matters is the product of coefficients realized by moving through the cycle. For a model which is purely cyclical the stability condition is based on the "worst case" cycle, it is deterministic and corresponds to that of the skeleton process, and it is very much like that of the TAR(l) process with delay discussed in section 5. The model may also have, however, situations where one or more of the rays of type (17) actually lie on a threshold. In such a case, Xt can fall on either side of the threshold, and thus into one of two possible regions, at random but depending on both the present error et and the past errors e t _i,..., et-q. If Jt denotes the region that Xt is in then {(Jt, Ut)} behaves something like a Markov chain where the first component is one of a finite number of states and the second component is stationary. (If q = 0 then {Jt} itself is like a finite state Markov chain.) We relate {(Jt, Ut)} to such a Markov chain denoted, say, {(JtiUt)}. This chain is not necessarily irreducible or aperiodic but clearly every invariant measure is finite. Indeed it may be decomposed into a finite number of uniformly ergodic subprocesses. The coefficients |αχj| play the role of H(y) in this model. Now let G be any stationary distribution for {(Jt, Ut)} and define ΈJ = IRQ G(j,du). If (condition (15))
regardless of the choice of G then {(XuUt)} is geometrically ergodic aiίid, again, the condition is sharp. Because at least one ray lies on a threshold, the noncyclical models are special cases, but the stability condition for a noncyclical process can be quite different from that of nearby purely cyclical processes. See the parameter spaces for the TARMA(1,1) with delay 2 in Cline and Pu (1999c).
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Example 10. The third example combines the nonlinearity of piecewise continuous coefficient functions with a piecewise conditional heteroscedascity, a model called the threshold AR-ARCH time series: ξt = a(Xt-i) + b(Xt-i)et + c(et; X t -i), where a{x) and b(x) are piecewise linear, {c(ei a )} is uniformly integrable and Xt-i = (ξt-i, ,ζt-p) We further suppose a(x) and b(x) are homogeneous, b{x) is locally bounded away from zero except at x = 0, the thresholds are subspaces containing the origin and the regions of constant behavior are cones. Note that these assumptions need only hold asymptotically (in an appropiate sense) as x gets large. Once again, the Markov chain under study is {Xt} The basic idea on which we piggyback is that the process {Xt} collapsed to the unit sphere behaves very much like a Markov chain. The compactness of the unit sphere serves to make this chain stable and then the stability condition for the original chain can be computed. More specifically, define
S = α ( X t _ 0 + &(*_!)*,
X; = (ξl...,ξ*t-p+ι)
and θ*t = X*/\\X*t\\.
Then, due to the homogeneity of a(x) and 6(x), {0£ } is a Markov chain on the unit sphere and is uniformly ergodic with stationary distribution G, say. By the piggyback method, therefore, Xt has geometrically stable drift if
E (flog(\a(θ) + b(θ)e1\/\θι\)G(dθ)yj < 0. For a simple demonstration, suppose p = 1, a(x) = (αil x
+
P
p^y +P
log
(|α2
)
then {ξt} is geometrically ergodic. This example and generalizations of it will be considered fully in a forthcoming paper (Pu and Cline (2001)). Example 11. A very simple model which has not been analyzed fully is the ordinary TAR(2) model with additive noise, ξt = αi(X t -i)ξt-i + a2(Xt-ι)ξt-2
+ eu
where Xt-ι = (ξt-i^t-2) &nd αi(#) and a2(x) are piecewise constant. The precise stability condition is not known even when there is but one affine threshold. The results of this section, however, suggest that the key will be to identify an appropriate stochastic skeleton process to study.
165
NONLINEAR TS STABILITY
7. The Role of the Noise Distribution Tails. Spieksma and Tweedie (1994) pointed out how, with appropriate assumptions on the error distribution tails, an ordinary drift condition (such as (9) with V(x) = 1 + \x\) can be boosted to ensure geometric ergodicity of the process. We generalize the result as follows. Theorem 3 Assume {Xt} is an aperiodic, φ-irreducible T-chain in W and V : W —> [l,oo) is locally bounded. Suppose there exists a random variable W(x) for each x such that V{X\) < W(x) whenever XQ = x, {\W(x) — V(x)\ + er(w(x^~v(x^} is uniformly integrable for some r > 0 and limsupE (W(x) - V(x)) < 0. Then there exist s > 0 and V\(x) = esV^ ergodic (and hence geometrically ergodic).
(18)
such that {Xt} is V\-uniformly
Proof This follows directly from the drift condition for ^-uniform ergodicity (cf. Meyn and Tweedie (1993, Thm. 16.0.1)) and uniform convergence (cf. Cline and Pu (1999a, Lem. 4.2)). (See also the proof to Theorem 4.) D Essentially, this is the log-drift condition in another guise: if the test function in (10), for example, is replaced with V\{x) = esV^ with some sufficiently small s > 0 then (18) is a log-drift version of the condition. As a bonus, if V(x) is norm-like, satisfying ||x|| < V(x) < M +jfif||a;||, one gets strong laws and central limit theorems for all the sample moments (Meyn and Tweedie (1992), Chan (1993a,b)) and exponentially damping tails in the stationary distribution (Tweedie (1983a,b)). Example 12. For example, consider the FCAR(p) model discussed in section 3. If the noise term c(et;Xt-ι) is such that sup x E(er^eux^) < oo for some r > 0 then it frequently is possible to satisfy the requirements of Theorem 3 with a norm-like V(x). To illustrate how this can work, consider the FCAR(l) process, Xt = ξt = αi(6-i) + Φ t ; 6 - i ) with
-L < a\{x) < a\\x + αoi Ίix < -L,
, *
L > a\(x) > a\2X + αo2 if x > L, where a\\a\i — 1, a\\ < 0 and L < oo. We assume here that E(c(e\\ x)) = 0 for all x G R and sup x E(er^eux^) < oo for some r > 0. For the special case of equality on the right in (19) (the SETAR(l) model of Example 4), Chan et al (1985) showed {ξt} is ergodic if and only if 7 = 011^02 + «oi < 0. We thus assume 7 < 0. Let λi = λ^"1 = \J—a\\ and choose δ{ > 1, i = 1,2 so that -λiα O 2 + δχ- δ2 = X2OΌI + h - δ\ = λ 2 7/2. Define
V{x) = (\ι\x\ + δλ)lx<0
+ (X2\x\
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Then it is a simple computation to show that for some e > 0 and K < oo, V(Xι) - V(x) < (λ 2 lχ< 0 - λil x >o)c(ei; x) + X2j/2 + K\c(eγ,x)\l\c{ei]x)\>€\x\ χ ιs when |Xo| — \ \ sufficiently large, which satisfies the conditions of Theorem 3 with the limit in (18) being λ27/2. The time series is thus geometrically ergodic. On the other hand its skeleton, while stable, is not geometrically stable since a\\aγι = 1. In fact we would say both have only a linear drift. Tanikawa (1999) studied this example and Cline and Pu (1999b) looked at similar first order threshold-like models, but with a possible delay. Using a similar approach but with stronger stability conditions, Diebolt and Guegan (1993) studied multivariate examples and An and Chen (1997) investigated FCAR(p) models withp > 1. One of the drawbacks to a log-drift condition such as the one in Theorem l(iii) is that it guarantees geometric ergodicity only with test functions of the form V(x) = l-hλ(α;)||x|| r where r may be arbitrarily small and therefore it fails to imply needed limit theorems for sample moments. To be able to conclude Vί-uniform ergodicity with an exponential-like Vί, the condition must again be boosted and then the desired limit theorems will hold. Theorem 4 Assume {Xt} is an aperiodic, φ-irreducible T-chain in W and V : W —> [l,oo) is locally bounded and V(x) -> oo as \\x\\ -> oo. Suppose there exists a random variable W(x) for each x such that V(X\) < W(x) whenever Xo = x, {\ log{W{x)/V{x))\ + e ( ^ W ) r - ( ^ ) ) Γ } is uniformly integrable for some r > 0 and limsup£ (log{W(x)/V(x))) < 0.
(20)
IMI->oo
Then there exist s > 0 and V\{x) = e^v^s such that {Xt} is V\-uniformly ergodic (and hence geometrically ergodic). Proof For v > w > 1 and 0 < s < r, we have i {ew3~vS - 1) < ^ ( ^ - l) and log(w/v) < j fe - l j < 0. By the uniform integrability of {log(W(x)/V(x))}, truncation and uniform convergence (as s I 0),
Λi ((ii ((e("W-(v(*))« ("W(v(*)) __ Λ
< limsupE (\og(W(x)/V(x))lw{x)
Λ
+ e < -e,
(21)
167
NONLINEAR TS STABILITY For w > v > 1 and 0 < s < r/2, we have 0 < \og(w/υ) < - (ewS-υ° - l) < - (ewT~vT
-
and if wΓ-υr < K, v > M > 1 then ± (β 10 '-"* - 1) < g £ £ . By the uniform integrability of {e^ί*))'"^**))'}, truncation and V{x) -> oo as ||z|| ->• oo,
0 <
\imsupE(log(W(x)/V(x))lw{x)>v(x})
\\x\\-κx>
)M^)) _ Λ i
) <6,
(22)
for e > 0 and s > 0 small enough. From (20)-(22), therefore, we conclude there exists s > 0 small enough that limsupE (- (eWi»MV(*)) _ Λ IX o = \ Also, sup|| x ||< M J5 M v ( X l ) ) s
χ0 —xλ < oo for all M < oo, and hence geo-
metric ergodicity is assured with test function V\.
D
Example 13. We again consider an FCAR(l) model, ξt = «i(6-i) + c{et\it-ι), satisfying (19) but now we assume a n < 0 < anau < 1 and |c(ei;z)| < ci|a;|^|ei| where cx > 0, 0 < β < 1 and E(eη^) < oo for some η > 0. Let λi = y/-an, λ 2 = V~ α i2 and F(x) = 1 + (λil x
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Pham D.T. (1985). Bilinear Markovian representation and bilinear models, Stock. Proc. Appl. 20, 295-306. Pham, D.T. (1986). The mixing property of bilinear and generalised random coefficient autoregressive models, Stock. Proc. Appl. 23, 291-300. Pham, D.T. (1993). Bilinear times series models, Dimensions, Estimation and Models, ed. by H. Tong, World Scientific Publishing (Singapore), 191-223. Popov, N. (1977). Conditions for geometric ergodicity of countable Markov chains, Soviet Math. Dokl. 18, 676-679. Priestley, M.B. (1980). State-dependent models: A general approach to non-linear time series analysis, J. Time Series Anal. 1, 47-71. Pu, H.H. and Cline, D.B.H. (2001). Stability of threshold AR-ARCH models, tech. rpt., Dept. Stat., Texas A&M University (forthcoming). Quinn, B.G. (1982). A note on the existence of strictly stationary solutions to bilinear equations, J. Time Series Anal. 3, 249-252. Spieksma, F.M. and Tweedie, R.L. (1994). Strengthening ergodicity to geometric ergodicity for Markov chains, Stock. Models 10, 45-74. Tanikawa, A. (1999). Geometric ergodicity of nonlinear first order autoregressive models, Stock. Models 15, 227-245. Tj0stheim, D. (1990). Non-linear time series and Markov chains, Adv. Appl. Probab. 22, 587-611. Tj0stheim, D. (1994). Non-linear time series: a selective review, Scand. J. Stat. 21, 97-130. Tj0stheim, D. and Auestad, B.H. (1994a). Nonparametric identification of nonlinear time series: projections, J. Amer. Stat. Assoc. 89, 1398-1409. Tj0stheim, D. and Auestad, B.H. (1994b). Nonparametric identification of nonlinear time series: selecting significant lags, J. Amer. Stat. Assoc. 89, 1410-1419. Tong, H. (1981). A note on a Markov bilinear stochastic process in discrete time, J. Time Series Anal. 2, 279-284. Tong, H. (1990). Non-linear Time Series Analysis: A Dynamical System Approach, Oxford University Press (London). Tuominen, P. and Tweedie, R.L., (1979). Markov chains with continuous components, Proc. London Math. Soc. (3) 38, 89-114. Tweedie, R.L. (1975). Sufficient conditions for ergodicity and recurrence of Markov chains on a general state space. Stock. Proc. Appl. 3, 385-403. Tweedie, R.L. (1976). Criteria for classifying general Markov chains. Adv. Appl. Probab. 24, 542-574. Tweedie, R.L. (1983a). Criteria for rates of convergence of Markov chains with application to queueing and storage theory, in Probability, Statistics and Analysis, London Math. Society Lecture Note Series, ed. by J.F.C. Kingman and G.E.H. Reuter, Cambridge Univ. Press (Cambridge). Tweedie, R.L. (1983b). The existence of moments for stationary Markov chains, Adv. Appl. Probab. 20, 191-196.
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Institute of Mathematical Statistics LECTURE NOTES — MONOGRAPH SERIES
TESTING NEUTRALITY OF mtDNA USING MULTIGENERATION CYTONUCLEAR DATA Susmita Datta Department of Mathematics and Statistics Georgia State University Abstract The neutrality theory of evolutionary genetics assumes that DNA markers distinguishing individuals and species are neutral and have little effect on individual fitness (Kimura, 1983). Under this hypothesis, the action of genetic drift or genetic drift in combination with mutation or migration can be used to describe the evolution of most DNA markers. In recent years, scientists have set up experiments to collect cytonuclear data over several generations to test whether the empirical evidence is consistent with this theory. In this paper, we review the existing statistical tests for neutrality based on such data and propose a new test that we believe is vastly superior. The new test arises from the likelihood theory after embedding the neutral model in a larger class of selection models, where the selection effect takes place due to a difference in fertility of various gametes. A power study based on Monte Carlo simulation is presented to demonstrate the superior performance of the new test.
1
Introduction
A major debate amongst evolutionary geneticists in recent years is whether most DNA markers distinguishing individuals and species are neutral and have little effect on individual fitness (Kimura, 1983). As a profound application of this theory, DNA sequence differences between extant species have been used to reconstruct the history of life. The classical theoretical developments of random genetic drift is built around this assumption. Under this hypothesis, the action of genetic drift or genetic drift in combination with mutation or migration can be used to describe the evolution of most DNA markers. The recent attacks on the neutrality theory are twofold. Firstly, it has been pointed out that in some cases non-neutral models can also explain behavior consistent with empirical evidence. For example, Gillespie (1979) showed that his model of selection in a random environment has the same
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stationary distribution as the infinite allele neutral model. Therefore, the agreement between observations and that predicted by the infinite allelic model noted by Fuerst et al. (1977) can be used with equal strength to support Gillespie's model of natural selection. In another context, Rothman and Templeton (1980) showed that, under some departure from the model assumptions, a neutral model (Watterson, 1977; Ewens, 1972) can yield frequency spectra and homozygosity similar to those expected from heterosis. In addition to the above results, a number of recent experiments suggest apparent non-neutral behaviors of mtDNA markers (Clark and Lyckegaard, 1988; MacRae and Anderson 1988; Fos et al., 1990; Nigro and Prout, 1990; Pollak, 1991; Arnason, 1991; Kambhampati et al., 1992; Scribner and Avise, 1994a, b; Hutter and Rand, 1995; etc.). Singh and Hale (1990) suggested that the apparent "non-neutral" behavior may also be caused by mating preference and that any attempt to understand the role of selection on mtDNA variants should first begin with simpler conspecific variants rather than with interspecific variants; however see MacRae and Anderson (1990), Jenkins et al. (1996). Multi-locus empirical comparisons have been undertaken by Karl and Avise (1992; also see McDonald, 1996), Berry and Kreitman (1993), McDonald (1994). In view of these recent experimental developments it is important to test whether the apparent non-neutral behavior of the markers are indeed statistically significant. Consequently it is more important than ever to devise appropriate statistical tests for testing the neutrality of a mtDNA marker. As we will see in Section 3, the existing statistical tests are often too limited to take full advantage of the multi-generation cytonuclear data that are now available. As a result, a new test based on the recent works by Datta (1999, 2001) is proposed. This test is based on an approximate likelihood for the full available data constructed from a broad parametric selection model and is therefore expected to perform well in practice. The data collection scheme and the underlying model of random drift for genetic evolution is introduced in the next section. This neutral model serves as the null model for the statistical tests which are introduced in Sections 3 and 4. A numerical power study based on Monte Carlo simulation is reported in Section 5. The paper ends with some concluding remarks in Section 6.
2
Data Collection Scheme and the Random Drift Model
In recent kitty-pool experiments, there are two potential sources of variation in cytonuclear frequencies, namely, genetic sampling variation and statistical sampling variation (Weir, 1990). Genetic sampling variation arises
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from genetic drift, the sampling of gametes from a finite breeding pool of individuals in nature to constitute the next generation. Statistical sampling variation arises from sampling individuals from a population and using the genotypic frequencies from the sample in subsequent calculation. In Datta et al. (1996), test statistics based on cytonuclear disequilibria were constructed which can account for both sources of variation. The sampling scheme is described below. Such sampling schemes were introduced by Fisher and Ford (1947) and subsequently considered by Schaffer et al. (1977). Kiperskey (1995) also collected data on the fruit fly Drosophila melanogaster following such a scheme. We feel that these types of sampling schemes will become increasingly important in prospective tests for selection (White et al., 1998) using molecular markers in which a cytoplasmic marker is included as a control. Consider a population propagating through discrete non-overlapping generations. Although this is a simplifying and restrictive assumption, it can be achieved for an experimental population with specially selected species, such as Gambusia and fruit flies. At each generation, a portion of the adult population is collected by simple random sampling and sent for genotyping after they form the next generation; eggs by random mating. The eggs are then collected and placed in a cage to form the next generation. Thus, in this case, only the sample genotypic relative frequencies are available and are therefore subject to the additional source of sampling variation. We let g denote the number of consecutive generations from which samples were drawn. Throughout the rest of the paper, we will simultaneously concentrate on a nuclear site with possible alleles A and a and a cytoplasmic site with possible alleles Cand c. The various relative frequencies at the genotypic and the gametic levels are indicated in Tables 1 and 2, respectively. Note that since the cytoplasmic marker is only maternally inherited, its representation remains the same at both levels. Also, if needed, we will denote the generation number (i.e., time) in parenthesis and the corresponding quantities at the sample level will be indicated by the hat notation. Table 1 Genotypic frequencies Nuclear Allele Cytoplasm AA Aa aa Total C V2 P3 q Pi c P4 P5 Pe 1-q V u w 1 Total
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176
Table 2 Gametic frequencies
Cytoplasm C
Nuclear Allele A a Total eι
c
Total
q
e4 P
l-q 1
Under the action of genetic drift alone, the evolution of the population through generations can be modeled by the following Markov chain. Under the RUZ (random union of zygotes) model (Watterson, 1970), the probability of observing an offspring which received gametic types / and m, respectively, from the two parents is e/e m . Thus, the probability distribution of the counts X(t + 1) = (Xn(t +1), , Xu(t + 1)) in generation t + 1,given Ww> the gametic combination counts up to time ί, is multinomial and is given by (1)
(2) where JVi+i = Σ/,m x /m(^+l) is the size of the ί+1 generation. Finally note that this in turn determines the distribution of the genotypic and the gametic proportions p(t + 1) and e(t + 1), since they are just linear combinations of the x(t + l);viz, pk(t) = {Σf,m<*fmkXfm{t)}/Nt and φ) = ΣkβikPk(t) The coefficients a and β are given in Tables 3 and 4, respectively. For example, since the mtDNA is only maternally transmitted, the genotype AA/C can be formed by either A/C from the father and A/G from the mother, or by A/c from the father and A/C from the mother leading to = {xn(t)+X2i{t)}/Nt.
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Table 3 The coefficients aifmk
f
m
1
2
k 3
4
5
6
1 2 3 4
1 0 0 0
0 0 1 0
0 0 0 0
0 1 0 0
0 0 0 1
0 0 0 0
1 2 3 4
0 0 0 0
1 0 0 0
0 0 1 0
0 0 0 0
0 1 0 0
0 0 0 1
lor 2
3or4
Table 4 The coefficients i k 1 2 3 4
5 6
3
1 1 1/2 0 0 0 0
2 0 0 0 1 1/2 0
3 0 1/2 1 0 0 0
4 0 0 0 0 1/2 1
Existing Neutrality Tests Based on Multigeneration Data
Here we review two existing tests of neutrality based on multigeneration data. The first one, due to Schaffer et al. (1977), compares the relative frequencies at a single locus with that expected under random drift over the generations. The test due to Datta et al. (1996) takes advantage of simultaneous data collected at a nuclear site and a cytoplasmic site over generations and compares the pathways of association measures, called the cytonuclear disequilibria, with their expected values over time under random drift. Other existing tests for neutrality generally compare various empirical characteristics based on the very last generation data with the corresponding
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asymptotic value reached at the equilibrium distribution under random drift. The obvious criticisms of such methods are (i) they don't take full advantage of the multigeneration data and (ii) the theoretical basis is questionable unless the population has been in existence for a long time.
3.1 The Schaffer-Yardley-Anderson
tests: This test is a modifica-
tion of a classical test due to Fisher and Ford (1947). They considered the variance stabilizing angular transformation ( 2 sin~ ^relative frequency ) of the proportions at a single locus and compared them with their constant expected value under the action of genetic drift leading to the asymptotically chi-squared distributed test statistic:
where
^ _ l'W~ιY ~ 1W-1Γ Y is the vector of transformed relative gene frequencies, 1 is the vector of ones and W is the matrix whose elements are given by μ
z-1
,
k-l/N
k=l
i y k
j=ϊ \
,*
i <j . ±y
3 J
In an effort to improve the power properties of their test, Schaffer et al. (1977) also proposed an alternative test which effectively tests for linear trend in the transformed frequencies. Although such a selection model may be hard to justify biologically, this approach does lead to a usable test statistic.
3.2 The disequilibria test due to Datta et al.: The Schaffer et al. tests do not make full use of cytonuclear data because they were constructed for tracking the information at a single locus. Datta et al. (1996) proposed testing the dynamics of the sample cytonuclear disequilibria coefficients (see Arnold 1993) with those expected under a drift model. This resulted in a test statistic of the form
T2 = (D-μYΣ^φ-μ) which has an approximate chi-squared distribution under the null hypothesis of random drift. Here D is the vector of sample cytonuclear disequilibria, μ is its expectation under the neutral model of random drift and Σ is its estimated variance-covariance matrix. The above test is somewhat difficult to implement in the sense that the formulas for Σ are complicated. Moreover its power properties may be poor due to its omnibus nature.
NEUTRALITY
4
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OF mtDNA
A New Test Based on a Selection Model
In order to take full advantage of the multigeneration cytonuclear data, very recently Datta (2000) considered a fairly broad selection model that includes the neutrality model of random drift as a special case. The selection effect takes place because of a difference in the fertility of various gametes. We propose the resulting likelihood based score test for testing the neutrality hypothesis. Not only does it arise very naturally, it incorporates the entire cytonuclear information present in the data; furthermore since it is derived from embedding the null hypothesis of random drift into a fairly rich parametric alternative selection model, it should enjoy reasonable power properties at least when the selection model holds. A simulation based power comparison study reported in the next section shows that this is indeed the case. Consider the following selection model as an alternative to the random drift model describing the evolution of the population. The probability of observing an offspring which received garnetic types / andra, respectively, w e from the two parents is ef(w)em(w)where eι(w,t) = Wieι(t)/ yΣ j j{t))\ here W{ denote the relative fertility of gametic type i, 1 < i < 4. Therefore, the distribution of the counts x(t + 1) given the t-th generation is given by (1) with the product ef(t)em(t) replaced by ej{w, t)em(w, t). Note that when W{ = 1/4, one has the random drift model. Therefore, a test of neutrality can be based on the score statistic s(wo), with wo = (1/4, , 1/4). Since s, the derivative of the log-likelihood based on the population gametic relative frequencies, is not computable from the observed data, Datta (2001) suggested using an approximate version of it obtained by replacing them with the corresponding sample versions. This results in additional terms for the variance-covariance matrix, all of which can be consistently estimated from the observed data. One can show that the approximate log likelihood has a simple closed form expression given by g-i
6
Άw) = Σ Σ Nt+ιPk(t + 1) log(ifc(ti;,i)) t=l
k=l
Lι(w,t) = e\(w,t) +
eι(w,t)e2{w,t),
L2{w,t) = 2e1(ϊi;,ί)e3(iί;,t) + e2(w,t)es{w,t) + eι(w,t)e4(w,t) Ls(w, t) = e\(w, t) + e3(w, t)e4(tu, t),
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DATTA
t) = ej(w,t) +es(w,t)eA(w,t)
1
and βi{w,t) = ei{t)wi/ ί Σej{t)wj J , 1 < i < 4. See Datta (2001) for the details of the algebraic calculations. Of course, the approximate score is defined as s(w) ^ (d/dw) I (w) where we interpret it as a function of w = (wι,W2, ws) ( i.e., replace w^ by I — wι — w2 — w^). Datta (2001) was able to calculate the estimated asymptotic variancecovariance matrix of s given by Σ y = (d/dw)(s(w))\w=g
+ C f d + CξC2 + ••• +
CjCg,
where
ds{w;p{l), -,p(g)) dP(t)
-1I/2
\{diag{p(t))-p(t)p(t)T)/nt]
1 < < ^ 9 Therefore, a test statistic for the neutrality hypothesis is given by T = S {WQ)Σ^S{W ) with w0 = (1/4,1/4,1/4). The neutrality hypothesis would be rejected if T exceeds Xχ_Q(3). T
0
5
Power Studies
We now report the results of a simulation study where we compare the power of Datta's (2001) test with those of earlier tests by Schaffer et al. (1977). The experimental setup is as follows. The w are parametrized by a single parameter μ so that w\ = w2 = 1/2 - μ; ^3 = W4 = μ. We simulated 2000 multigeneration samples each of g = 5 generations. The (constant) population size Nt equaled 1000 and (constant) sample size nt equaled 100. The initial population frequencies were given by pi — Pz — PA = P6 = 0; P2 = 0.5, p$ = 0.5. The counts x at the population level of successive generations are generated recursively using the multinomial model described in the second paragraph of Section 4. Next the genotypic and the gametic proportions are obtained by the formulas pk = Σ/,m afmkXfmlN and βi = Σk βikPk Finally, at every generation given the population p^ the sample pk are generated by multinomial (n; pi, • ,pβ) sampling. We simulated the powers of three different tests; (i) the omnibus test by Schaffer et al. for the mitochondrial locus, (ii) the linear trend test by Schaffer et al. and (iii) the new approximate score test by Datta described in the previous section. A nominal level of α = 0.05 was used for each case.
NEUTRALITY OF mtDNA
P _
181
*
0.8
1
•
Scor
s
SYA
1-
Unw
0.4
5-
0.2
s
ie
e
.
»
0.0
Λ
0220
0225
0230
0235
0.240
0.245
0.250
mu
Figure 5.1: Power of 5% tests at selected values of μ Figure 5.1 describes the findings. To reduce computational time involved we computed the power at only four values at and near the null hypothesis value of μ = 0.25. The figure clearly illustrates the superior performance of Datta's approximate score test over the older tests. Whereas the power of this test reaches nearly one for μ = 0.22, the power for the other tests remain flat in the entire range of μ values under consideration.
6
Concluding Remarks
Testing the neutrality of DNA markers is an important problem in evolutionary biology. In recent years, experiments have been designed in a controlled setting where a population with discrete generation can be allowed to propagate at the same time random samples from each generation are collected. Often genotyping is done at two loci, say one nuclear and one cytoplasmic, simultaneously. Utilization of such multigeneration cytonuclear data in a set up where both genetic and statistical variabilities are present is a challenging problem. We present some recent work by Datta (2001) in this direction, where a neutrality test is constructed by correctly identifying an approximate likelihood for such a setup. A numerical comparison of power with earlier tests show great promise. It will be interesting to investigate the
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power properties more extensively covering a broad range of non-neutrality models, possibly going beyond the selection model considered here. Such a study is underway and will be reported elsewhere.
References
Arnold, J., 1993: Cytonuclear disequilibria in hybrid zones. Annu. Rev. Ecol. Syst. 24, 521-554. Arnason, E., 1991: Perturbation-reperturbation test of selection vs. hitchhiking of the two major alleles of Esterase-5 in Drosophila pseudoobscura. Genetics 129, 145-168. Berry, A. J. and Kreitman, M., 1993: Molecular analysis of an allozyme cline: alcohol dehydrogenase in Drosophila melanogaster on the east cost of North America. Genetics 134, 869-893. Clark, A. G. and Lyckegaard, E. M. S., 1988: Natural selection with nuclear and cytoplasmic transmission. III. Joint analysis of segregation and mtDNA in Drosophila melanogaster. Genetics 118, 471-481. Datta, S., 2001. Estimation of Selection Parameters using Multi-generation Cytonuclear Data, Biometrical Journal 43, 219-233. Datta, S., 1999: Hypotheses testing for different selection models using multigeneration cytonuclear data. In Proceedings of American Statistical Association, Biometrics Section, 157-161, Alexandria, USA. Datta, S., Kiparsky, M., Rand, D. M. and Arnold, J., 1996: A statistical test of a neutral model using the dynamics of cytonuclear disequilibria. Genetics 144, 1985-1992. Ewens, W. J., 1972: The sampling theory of selectively neutral alleles. Theor. Popul. Biol. 3, 87-112. Fisher, R. A. and Ford, E. B., 1947: The spread of a gene in natural conditions in a colony of the moth Panaxia dominula L. Heredity 1, 143-174. Fos, M., Dominguez, M. A., LaTorre, A. and Moya, A., 1990: Mitochondrial DNA evolution in experimental populations of Drosophila pseudoobscura. Proc. Natl. Acad. Sci. USA 87, 4198-4201. Fuerst, P. A., Chakraborty, R. and Nei, M., 1977: Statistical studies on protein polymorphism in natural populations. I. Distribution of single locus heterozygosity. Genetics 86, 455-483.
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Gillespie, J. H., 1979: Molecular evolution and polymorphism in a random environment. Genetics 74, 175-195. Hutter, C. M. and Rand, D. M., 1995: Competition between mitochondrial haplotypes in distinct nuclear genetic environments : Drosophila pseudoobscura vs Drosophila persimilis. Genetics 140, 537-548. Jenkins, T. M., Babcook, C, Geiser, D. M. and Anderson, W. W., 1996: Cytoplasmic incompatibility and mating preference in Colombian Drosophila pseudoobscura. Genetics 142, 189-194. Karl, S. A. and Avise, J. C, 1992: Balancing selection at allozyme loci in oysters: implications from nuclear RFLPs. Science 256, 100-102. Kambhampati, S., Rai, K. S. and Verleye, D. M., 1992: Frequencies of mitochondrial DNA haplotypes in laboratory cage populations of the mosquito Aedes albopictus. Genetics 132, 205-209. Kimura, M., 1983: The Neutral Theory of Molecular Evolution. Cambridge University Press, New York. Kiparsky, M., 1995: Cytonuclear genetics of experimental Drosophila melanogaster population. Unpublished Honor's Thesis, Department of Ecology and Evolutionary Biology, Brown University. MaCrae, A. and Anderson, W. W., 1988: Evidence of non-neutrality of mitochondrial DNA haplotypes in Drosophila pseudoobscura. Genetics 120, 485-494. MaCrae, A. and Anderson, W. W., 1990: Can mating preference explain changes in mtDNA haplotype frequency? Genetics 124, 999-1001. McDonald, J. H., 1994: Detecting natural selection by comparing geographic variation in protein and DNA polymorphisms. In Non-Neutral Evolution, B. Golding, Ed., 88-100, Chapman and Hall, New York. Mcdonald, J. H., 1996: Lack of geographic variation in anonymous polymorphisms in the American oyster Crassostrea virginica. Mol. Biol. Evol. 13, 1114-1118. Nigro, L. and Prout, T., 1990: Is there selection on RFLP differences in mitochondrial DNA? Genetics 125, 551-555. Pollak, P. E., 1991: Cytoplasmic effects on components of fitness in tobacco hybrids. Evolution 45, 785-790. Rothman, E. D. and Templeton, A. R., 1980: A class of models of selectively neutral alleles. Theor. Popul. Biol. 18, 135-150. Schaffer, H. E., Yardley, D. and Anderson, W. W., 1977: Drift or selection: test of gene frequency variation over generations. Genetics 87, 371-379.
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Scribner, K. T. and Avise, J. C , 1994: Population cage experiments with a vertebrate: genetics of hybridization in Gambusia fishes. Evolution 48, 155-171. Singh, R. S. and Hale, L. R., 1990: Are mitochondrial DNA variants selectively non-neutral? Genetics 124, 995-997. Watterson, G. A., 1970: The effect of linkage in finite random-mating population. Theor. Popul. Biol. 1, 72-87. Watterson, G. A., 1977: Heterosis or neutrality? Genetics 85, 789-814. Weir, B. S., 1990: Genetic Data Analysis. Sinauer Assoc, Sunderland. White, T., Marr, K. A. and Bowden, R. A., 1998: Clinical, cellular, and molecular factors that contribute to antifung drug resistance. Clinical Microbiology Reviews 11, 382-402.
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Institute of Mathematical Statistics LECTURE NOTES — MONOGRAPH SERIES
INFERENCE ON RANDOM COEFFICIENT MODELS FOR HAPLOTYPE EFFECTS IN DYNAMIC MUTATIONS USING MCMC. Richard M. Huggins1, Guoqi Qian1 Sz Danuta Z. Loesch2 department of Statistical Sciences, La Trobe University, Bundoora, 3083, Australia. 2 School of Psychological Science, La Trobe University, Bundoora, 3083, Australia. Abstract Modern genetic research involves complex stochastic processes and difficult inference problems and research in this area is necessarily a collaboration with geneticists and biologists. The major difficulty is in defining stochastic processes which are biologically meaningful yet amenable to analysis. To illustrate this we examine a class of random effects models for dynamic mutations. Dynamic mutations characterize several inherited disorders in humans. In these disorders a mutated segment of the gene typically increases in size as it is transmitted from generation to generation until the gene fails. Biological interest is in the effect of various genetic markers on the rate of expansion of the mutated segment and to what extent these markers describe alternate pathways. We concentrate on the widely studied fragile X disorder as there are data sets available for statistical analysis. We use heirarchical Bayes models fitted via MCMC methods to examine some data and hence determine a class of random coefficients, branching, time series models which have applications in genetical research.
1
Introduction
The realistic modelling of the stochastic processes occurring in biology quickly leads to analytically intractable models. However, these models may be of enormous practical importance. Here we examine a model for the recently discovered phenomenon of dynamic mutations, that lead to a number of genetic disorders. In these disorders rather than an on-off allele being transmitted from a parent to their offspring the mutation itself changes upon transmission. The mutation arises through expansion at a region of the gene, i.e. the insertion of extra genetic material in the form of trinucleotide
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repeats at that site. This induces instability at that site with the size of the expansion usually increasing from generation to generation. Ultimately the expansion becomes large enough to affect the functioning of the gene resulting in phenotypic expression of the disorder. A feature of these dynamic mutations is that they are clinically undetectable until the expansion crosses a threshold and phenotypically abnormal individuals arise. The fragile X Syndrome is the most widely studied dynamic mutation. It is a common X-linked genetic disorder associated with intellectual disability. The fragile X syndrome arises as the result of progressive CGG trinucleotide repeat expansion in the FMR1 gene, which culminates in the failure of gene expression. The mechanism for the expansion of the repeat size has not been determined. The fragile X syndrome is classified according to the number of CGG repeats. The premutation (55-200 repeats) and full mutation (200+ repeats) categories are unstable and some instability has also been reported within grey zone (35-55 repeats) alleles. Previously the rate of expansion of CGG repeats on transmission has usually been modelled as a function of the size of CGG repeat sequence on the maternal X chromosome. However, some molecular characteristics of the gene other than the size of the CGG repeat in this chromosome have recently been shown to affect the rate of expansion. These genetic covariates are certain combinations of microsatellite markers (haplotypes) flanking the repeat sequence, and the number and position of the AGG triplets which normally interrupt CGG repeats at intervals of 9-10 units. Eichler et al. (1996) have recently hypothesised that at least two different mutational pathways leading to the fragile X syndrome related to those genetic covariates are in action in the population. However, the data obtained by Dana et al (2000) from an Afro-American population showed that this hypothesis should be viewed from a broader evolutionary perspective. Several mathematical models for the transmission of fragile X have been proposed. These include comprehensive transmission models (Ashley and Sherman 1995, Morton & Macpherson 1992, Morris et al 1995), iterated branching models (Gawel and Kimmel 1996) and Bernoulli counting process models (Bat et al 1997). The model of Ashley and Sherman (1995) accounts for the dynamics of fragile X mutation by assuming the multi-step expansion of CGG repeats (meiotic expansion in either sex, and mitotic expansion restricted to somatic alleles of maternal origin). They also included population assumptions, such as selection against full mutation, as well as molecular mechanisms, such as the loss of AGG interspersions, which in their model constitutes the initial mutation in the FMR1 gene. These previous models were biologically meaningful but were difficult to analyse statistically and tended to become outdated as more data on molecular characteristics of the gene came to hand.
RANDOM COEFFICIENT MODELS
187
Huggins, Loesch & Sherman (1998) introduced a multi-step non-linear time series models for the transmission of dynamic mutations which could be analysed using standard statistical methods. They used a random intercepts model to examine the effects of haplotypes or genetic markers on the transmission of the mutation. Here we extend that model in several directions, with an emphasis on the effect of the genetic markers on the rate of transmission. Firstly, we use cubic splines to model the relationship between the length of the repeat sequence in offspring X chromosomes to that in the parent X chromosome. Secondly we allow the rate of transmission to be random, rather than just a random intercept. Available data consists of observations on several generations of affected families as, due to the lengths of human generations, it is not possible to collect DNA to construct longer chains. However, one purpose of our modelling is to be able to model distantly related affected individuals who are known to have a common ancestor. We illustrate the inference method using published data of Murray et al (1997) who report a variety of haplotypes which may be related to the rate of expansion in fragile X. The biological meaning of our results shall be discussed elsewhere, as will formal tests of hypotheses.
2
Notation
We label the observed haplotypes by h = 1,2,..., H. We suppose there are Nh families with haplotype /ι, labelled /ι/, / = 1,..., iV^. Let n^f denote the number of parents that produce observed offspring in family /&/, labelled /ι/fc, k = 1,..., rihf. Also, let Whfk be the number of offspring of individual hfk. The offspring of individual hfk are denoted by hfkl, I = 1,..., Whfk Note that individuals may be labeled both as parents and as offspring of their parents. This notation aids in constructing the conditional densities required below. In this paper, inference is conducted conditional on the initiating individual in each family, the observed family structure and the observed haplotypes. Further, the probands, or the individuals initially detected with the disorder in each family, have been omitted. This was done on order to reduce the ascertainment bias as the probands were usually detected by their having an extreme phenotype and hence genotype. Let Y be the vector of observations of the CGG triplet repeat lengths on all offspring. Namely, Y = {Yhfki : (Λ,/,M) e S], where S is defined by S = {(Λ,/,M): h = 1,2,-- ,£Γ; /|Λ = 1,2,--.,ΛΓΛ; k\hf = 1,2, -- , n Λ / ; l\hfk = 1,2, ,whfk.}. Here f\h is understood as the value of / given h.
188
3
HUGGINS, QIAN AND LOESCH
The Hierarchical Model
Our full model for the length of the CGG triplet repeat sequence in offspring I of individual k is of the general form { h)
(βh + β f )IF(hfk)}
+ δFIFζhfkl
+ σεh}ku
(3.1)
h = 1,... ,iϊ, f\h = 1,... ,ΛΓΛ, k\hf = 1,..., n Λ /, Z|/ι/fc = 1,..., wh}k, where sa n the C/ι/Jfc/' d tfifkis are independent normal random variables with 0 means and variance 1, Xhfk is a design matrix and IF(hfk) takes the value 1 if individual hfk is female and zero otherwise. The response g(Yhfkι) is taken m to be log log Yhfki this paper as this gave errors that appeared normally distributed, although other choices are possible. We suppose βh follows a common probability distribution for all individuals with haplotype h and βi ' follows a common distribution for all individuals in family / within haplotype h. The introduction of the sex effect allows us to mimic the Ashley-Sherman (1995) model and the subsequent model of Huggins et al (1998) which were two step models with an initial step common to transmissions from males and females, and a second step that only occurs in transmissions from females. This is difficult to directly model in a linear framework so instead we allow different rates in transmissions from males and females. Available data, see the plots of Huggins & Loesch (1998), suggest there is little difference between the haplotypes or families in transmissions from males and a single vector β is used to model this transition. The conditional mean Xhfk{β + (βh + βf^I^hfk)} of g(Yhfkι) as a function of the parameters and log Yhfk was modelled using cubic splines (Dierckx 1993). The corresponding B-splines are contained in Xhfk- As the present work is exploratory ten degrees of freedom were used in the cubic splines to allow flexible modelling. This gave similar results to models with different degrees of freedom (6, 8 and 14). Let m denote the number of columns of Xhfk- The main interest is in the posterior distributions of βh
and βf\
We will use the following prior distributions for the parameters /?, βh, βf \σ2 and tip:
2. βh - b2(βh\Σho) = DMVN(0, ΣΛO), 3. iβJ Λ) ~6i(i9j Λ) |Σ / o) = MyΛΓ(O1Σ/o), 4. σ 2 ~ 6 4 ( σ > , λ ) = = IGa(i//2,i/λ/2), 5. 4 ~ 6 5 ( 4 1 ^ , λ F ) = IGa(ι/F/2, I/
h = 1,..., £Γ, f\h = 1,... ,JVΛ, Λ = l , . . . ,
189
RANDOM COEFFICIENT MODELS
which are all assumed to be independent. Here MVN denotes the multivariate normal distribution, IGa the inverse Gamma distribution (e.g. Robert 1994, p. 153). The values of v, λ, up and Xp do not have any significant effect on the analysis so will be specified in the study (see Appendix A). The hyperprior distributions for the hyper-parameters in the above prior distributions are taken to be: 1. βo ~ Wo|&,Σ) = DMVN{b,Σ), 2. Σ o - W - H ξ o + m + l^oiϊo),
ξo>m
ι
3. Σfco ~ W- (ξh0 + m + l,ξhoRhθ), ι
4. Σ/o - W- (ξf0
+ m + l,ξ/OΛ/o),
ξhx> > m, ξ/o > m,
which are also assumed to be independent. Here W7^1(ξ. + m + l.ξ.R.) denotes an inverted Whishart distribution for an m x m random matrix Σ. with degrees of freedom £ + m + 1 and positive definite matrix R. It can be shown that ^ ( Σ " 1 ) = R~ι and E(Σm) = {(£ - m - ljξ.β.}" 1 if these exist (Muirhead 1981, p.113). The values of &,Σ,fθj-Ro?fΛθ?Λ/ιθjf/o a n d Rfo will be specified in Appendix A. We denote the last three densities by wo(Σo|ξo,i?o), u>hθ(Zho\ξhθ,Rhθ) and^ /o (Σ/o|ξ/o,Λ/o) respectively. In order to simplify the presentation, we use Θ and 7 respectively to denote the parameters and hyper-parameters in the hierarchical model defined here. Namely, Θ = ( / ^ / ^ / ^ σ 2 , ^ ) * and 7 = (/3b,Σo,ΣΛO,Σ/o), where Ph — vPi?
7 P/f J 5 P/ — vP/
5
? P/
a n α
P/
— vPi
/ι = 1, , H. Note that Θ is a vector of dimension (1 + H + Σ Λ ^ I Nh)m + 2 and 7 is an m x (1 + 3m) matrix. The equation (3.1) together with the prior distribution of Θ and hyperprior distribution of 7 comprise a hierarchical random effects model for the CGG triplet repeat sequence. In order to make inference about Θ and 7, and in particular βh and βj ' from the data, we need the posterior distributions of βh and βί '. Because of their mathematical complexity we will not be able to make inferences directly from these posterior distributions. Rather we will first generate a sample from these distributions and then make inferences from the sample. The Markov chain Monte Carlo (MCMC) technique has shown to be powerful in simulating a sample from those probability distributions which are analytically intractable. Recall that the basic idea of MCMC is to use a relatively simple transition probability kernel to generate a Markov chain in such a way that its invariant distribution is that from which we want to generate a sample. After a sufficient number of generations of the chain have been simulated, subsequent generations can be regarded as a sample from the target distribution. Two most basic algorithms used in MCMC methods are Gibbs sampling and Metropolis-Hastings
190
HUGGINS, QIAN AND LOESCH
algorithm. We use a mixture of these two algorithms which is called MCMC block-at-a-time algorithm (Chib and Greenberg, 1995). Several methods are available (Robert 1998) for monitoring the convergence to stationarity of the resulting Markov chain. We employ the GelmanRubin statistic (Gelman and Rubin 1992) which measures the correlation between the within- and between-chain variations of the simulated multiple Markov chains. When the Gelman-Rubin statistic becomes very close to 1 (usually less than 1.2 or 1.1 is enough in practice), the chains can be regarded as having achieved convergence. Once a sample has been generated from the joint posterior distribution, it can be examined to detect the random effects of haplotypes and families. The sample can also be used to simulate the posterior predictive distribution for the response variable CGG repeats which, after comparison with the true CGG observations, allows determination of the goodness of fit of the model. The various joint and conditional densities and the MCMC procedure used to fit the model are described in the appendices.
4
Results
The data of Murray et al (1997) contain observations on CGG repeat sequences for 124 individuals and their parents after the probands were omitted. The remaining 124 individuals are the offspring of 86 observed parents who come from 57 different families, nested in 18 different haplotypes. In addition, 10 of the 86 observed parents are fathers who between them have 18 offspring. When applying the hierarchical model of section 3, the parameter vector Θ contains 762 components and the hyper-parameter 7 is a 10 x 31 matrix. For each of these parameters we generated 3 Markov chains of length 10,000 from which the posterior samples were formed. We first check the convergence of the simulated Markov chains. It was found that for the current model at most 2400 transitions would be sufficient for the simulated Markov chain to be stationary. In the simulations the slowest convergence occurred at the Markov chain of Θ(88) = /?s (8) (component 8 of haplotype 724) among all parameters and at 7(6,17) = E^o^β] (the 6th diagonal element of Σ^o) among all hyper-parameters. Figure 1 displays the sub-chain of a simulated Markov chain (by filter [fc/50], i.e., taking every 50th value) for each of /?s(8) and Σ^oίθjθ) and their Gelman-Rubin statistic value sequences based on the 3 parallel chains. To form a posterior sample for each parameter or hyper-parameter, we discard the first half of each of the 3 generated chains and combined the rest into one sequence; then we filter this sequence by the operator [Λ /50] and take the resulting sequence of length 300. Shown in Figure 2 are histogram densities of the posterior samples for the 10 components of the haplotype
RANDOM COEFFICIENT MODELS
191
tt> 6
I G-RvaluβsforSigr ω
^
y-1.2 " V-1-1 40
100
160
Figure 1: Row 1 gives Markov chains generated for β$(8) and Έho(6,6). Row 2 gives the corresponding Gelman-Rubin statistic values based on the three parallel chains.
8 effect 0 8 (the 81st-90th elements of Θ, i.e. Θ[81 : 90] and the 10 components of the family effects β[2) = Θ[261 : 270] (effects of the first family in the second haplotype which are the 261-270th components of Θ). These histograms are also typical of other haplotype and family effects. The haplotype effects can be analysed by examining whether or not there is any heterogeneity among the marginal posterior distributions of {βh(ϊ), h = 1, , 18} (i = 1, , 10). Shown in the first column of Figure 3 are the Xbar-chart and S-chart with 95% confidence level for posterior samples of {0i(8), ,0is(8)}, and the histogram density and the QQ-plot for the corresponding posterior means. The other two columns of Figure 3 are for {0i(6), ,/?i8 (6)} and {0i (3), ,0is(3)}. Figure 3 gives evidence of haplotype effects in the expansion process. The family effects given the haplotype effects can be similarly analysed based on the marginal posterior distributions of βf(i) (i — 1, , 10). The three columns in Figure 4 give the results of these effects from the posterior samples of 0/(8) 's, 0/(4)'s and 0/(1) 's respectively. Again family effects are evident in Figure 4. The goodness of fit of the model can be assessed by comparing the response observations g(Y) to their posterior predictive distributions (Gelman et al 1995, sec. 6.3). For each response observation g(Yhfki) a sample of size 300, regarded as the replicates of g(Yhfki) which could have been observed,
HUGGINS, QIAN AND LOESCH
20
20 40 60
0
0
40 60
192
1 A3 A bθta_8(3)
s
Jh J L
°
•10 bita.Vf
s
1
°
"
s
5 -10 -5 0 5 10 bβta_8(7)
•10
0
1
jjj^H
-5bβ°te_8δ)10
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s
L
3 d
H
^
—
-
0-5 0 5 10 bβta_8(10)
S
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o
5 bθta_1Λ{(2)}(5)
bθta_1Λ{(2)}(3)
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i
b 5 βtL8?8) 1 °
s
w -5
bθta_8(5)
S
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bθta_8(4)
s
A!
jL
A (2)
Figure 2: Histograms for all the 20 components of βs and β\
II
I„
»^umber beyond
V\/ \/\
- Λ
ii
-o Λ Λ beyond ϊmits=0
Λ. ^
Number beyond id bmi(s=0 bmi(s=0
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\ /°
A
V-
π
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\/
Number beyond limils=2
"
I:
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o
V
'
/
"
•
%
-
.
Nurnber bβvond lirr |s=2
11
Figure 3: Effects of haplotype factors evaluated at components 8, 6 and= 3.
RANDOM COEFFICIENT MODELS
1101
^.. ^..^.. . X Al
Number beyond Km ls=2
Number beyond limits=4
s Chart lor bθta.f.8
I: " ^ I3
193
1 4 7 10 13 I t in
s Chart for bela.f.4
ΐ
s Chart (orbβta.1.1
g oil "juj'jj ib^'jis,"
111
πv*ϊ
κ
N U j mber beyond Bmits=0
π Figure 4: Effects of family factors evaluated at components 8, 4 and 1.
was generated from its posterior predictive distribution. Then the Bayes pvalue was calculated for each sample, which is the proportion of the replicates that are greater than g{Yhfki) The histogram density for the replicates of log log Yg, which is typical for all 124 response observations, is given in Figure 5. A histogram of the 124 Bayes p-values is also given in Figure 5. Since most of the Bayes p-values are very close to 0.5 (all but one are between 0.4 and 0.563), it implies that the response observations are typical under the posterior predictive distributions. In addition, we provide in Figure 5 the plots of log log Ynew IY — the sample means of the posterior predictive distributions against= log log Y, and £?(loglog Y|Θ p o 5 ) — the fitted response values using the posterior means of the distributions of the /?'s against log log Y. These plots show the reasonable fit of the proposed model to the data which is also supported by the values of the goodness of fit statistic computed from (2) below. Actually it was found that || loglog Y-loglog Yne™|Y||2 = 14.10 and 11 log log Y - E(loglog Y | Θ p o 5 ) | | 2 = 7.26. However, the histogram density in Figure 5 shows that the posterior predictive distribution of Y has a quite wide range and a large variance, particularly considering the nature of a loglog( ) transformation for the response Y. This implies that the proposed model has a large variation in its predictability although it is not the main interest of this paper. One could possibly obtain better predictions if another transformation g(Y) or a discrete model such as a Poisson distribution for Y were used. Finally we propose to evaluate the goodness of fit of the model by the
HUGGINS, QIAN AND LOESCH
194
summary(bayesPIO) Min. 1st Qu. Median Mean 3rd Qu. Max. 0.317 0.477 0.497 0.497 0.517 0.563
-15-11-7-3 1 5 9 13 17 Histogram density of log(log(Y_9)) from a
0.25 0.31 0.37 0.43 0.49 0.55 0.61 Histogram for θayes p-vakies with individual
v obs. parent is father t-obs. parent is mother l
••
+ obs. parent is father +obs. parent is mother
k>g(log(Y))
Figure 5: Model assessment based on posterior predictive distributions.
following statistic N
N
i=l hfkl
Var(Yhfkl\θi)
(4.1)
where θ i , , θ # is a posterior sample of θ . Although no rigorous justification is available, it sounds sensible to approximate T by a χf 24 distribution without being too erroneous. Based on the posterior θ sample generated in our study we found T = 87.26, which corresponds to 0.5-percentile of a χ{24 and thus indicates that the proposed model gives an adequate fit.
5
Discussion
Many of the advances in inference for stochastic processes over the past few decades have arisen from branching processes and time series models. A population model for the transmission of dynamic mutations combines time series models with branching processes, for, as well as (3.1) holding the number of offspring Whfk of individual hfk has a distribution that depends on both the sex of individual hfk and the value of Yhfk- The outstanding problem is to find conditions under which the population model has a stationary distribution. We have concentrated on developing and fitting time series type models for the transmission of a dynamic mutation given the observed haplotypes
RANDOM COEFFICIENT MODELS
195
and family structures. The model can be viewed as an extension of the simpler bifurcating autoregressive models for cell lineages. The work on cell lineage studies starting with Cowan (1984), Cowan &: Staudte (1986) and others considers the bifurcating autoregressive process for cell lineage studies. Cell lineage trees arise from the binary splitting of cells and the processes of interest are time series, typically low order autoregresive models, down lines of descent with correlated errors for sister cells and in later models (Huggins & Basawa 1999) correlations between individuals in the same generation. Bui & Huggins (1999) considered random effects models for the bifurcating autoregressive(l) model. The processes of interest here have a random number of offspring rather than just the two of the bifurcating autoregressive process and the models down each line of descent are more sophisticated than the ARMA type processes. Moreover, individuals with a given identified haplotype may differ at other gene sites, which naturally gives rise to the random effects models. Hence we take the transition rates to be random, which are common for individuals in the same families and there is communality between unrelated individuals with the same haplotype. Markov models are typically used to model the transmission of a characteristic from parent to offspring. That is, the genetic make up of the offspring only depends on that of the parents. The indiscriminant use of such Markov models may be unrealistic in the branching situations that occur in family studies. For example, in related work on cell lineage studies, Staudte et al (1996) determined that the correlation between cousins in the data examined by them was larger than what was predicted by AR(1) type Markov models. In Markovian AR(1) models for cell lineages, correlations drop off as powers of the mother-daughter correlation θ. That is, mother-daughter correlation is 0, the= sister-sister correlation is θ2 (plus environment effects) the cousin-cousin correlation is 04 etc. Huggins & Basawa (1999) proposed several models which allow higher correlations between cousins and other more distant relatives including an AR(2) type model as well as random effects models of generation effects. This situation may also occur in dynamic mutations unless genetic covariates that affect the expansion rates are taken into account. This motivated our hierarchical random effects model. The models examined here are based on transmissions over one or two generations and may not reflect the full complexity of the dynamic mutations. Moreover, the processes are sparsely observed and as the process is unobserved in its initial stages, there is little information concerning the mutation rate currently available. The nested random effects, which depend on haplotypes that are themselves evolving according to some stochastic process, add another level of complexity. However, the haplotypes occur on a portion of the gene which does not appear to code for a protein hence they should not be exposed to selection so that their evolution should be depen-
196
HUGGINS, QIAN AND LOESCH
dent only on random mutations and rare recombinations and be simpler than that of the the FMR1 gene itself. Future work will involve the collection and modelling of data on distantly related affected individuals, where the evolution of the haplotypes will need to be considered. The strength of the relationship between individuals will be determined either through family trees or through genetic markers with known mutation rates. It is not necessary to use MCMC to estimate random effects although it was convenient in the present example. For example, Park & Basawa (2000) have developed an optimal estimating function approach. However, they have not yet fully developed the inferential procedures. The use of cubic splines has advantages in that the models are linear and may to some extent be regarded as non-parametric. Moreover, it was not necessary to introduce a threshold as in Huggins et al (1998). However, the non-linear models of Huggins et al (1998) did have some biological advantages in that they more naturally modelled the expansions in the meiotic and mitotic phases. In the non-linear case it was possible to let the parameters in the model depend on the size of the parents repeat sequence which is more difficult in linear models. The increasing interest in molecular genetics will result in new and complex stochastic processes. However, as in cell lineage studies and the example considered here, these new processes are combinations of familiar simpler stochastic processes with perhaps extended error structures. Nevertheless, it appears certain that many new problems in statistical inference and applied probability will arise in this area. Acknowledgements This research was supported by NICHID grant # HD36071 and an Australian Research Council small grant.
References [1] Ashley, E.A. & Sherman, S.L (1995) Population dynamics of a meiotic/mitotic expansion model for the fragile X syndrome. Am. J. Hum. Genet 57: 1414-1425. [2] Bui, Q.M. & Huggins, R.M. (1999) The random coefficient bifurcating autoregression model in cell lineage studies. J. Stat. Plan. & Inf. 81; 253-262. [3] Bat O, Kimmel M, & Axelrod DE (1997) Computer simulation of expansions of DNA triplet repeats in the fragile X syndrome and Huntington 92s disease. J.Theor.Biol. 188: 53-67
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[4] Chib, Siddhartha and Greenberg, Edward (1995) Understanding the Metropolis-Hastings Algorithm American Statistician V. 49, No. 4 327335. [5] Cowan, R. (1984). Statistical concepts in the analysis of cell lineage data. Proceedings of the 1983 Workshop on Cell Growth and Division., 18-22, LaTrobe University. [6] Cowan, R. and Staudte, R.G. (1986). The bifurcating autoregression model in cell lineage studies. Biometrics. 42, 769-783. [7] Dana C. Crawford, Charles E. Schwartz, Kellen L. Meadows, James L. Newman, Lisa F. Taft, Chris Gunter, W. Ted Brown, Nancy J. Carpenter, Patricia N. Howard-Peebles, Kristin G. Monaghan, Sarah L. Nolin, Allan L. Reiss, Gerald L. Feldman, Elizabeth M. Rohlfs, Stephen T. Warren, and Stephanie L. Sherman (2000) Survey of the Fragile X Syndrome CGG Repeat and the Short-Tandem-Repeat and SingleNucleotide-Polymorphism Haplotypes in an African American Population. Am. J. Hum. Genet. 66 480-493. [8] Dierckx, P. (1993). Curve and surface fitting with splines, Clarendon: New York. [9] Eichler, E.E., Macpherson, J.N., Murray, A. Jacobs, P.A., Chakravarti, A. and Nelson, D.L. (1996) Haplotype and interspersion analysis of the FMR1 CGG repeat identifies two different mutational pathways for the origin of the fragile X syndrome. Human Molecular Genetics. 5 319-330. [10] Gawel B & Kimmel M(1996) The iterated Galton-Watson process. J.Appl.Prob. 33: 949-959. [11] Gelman, A. and Rubin, D.B. (1992). Inference from iterative simulation using multiple sequences (with discussion). Statistical Science 7,457511. [12] Gelman, A., Carlin, J.B., Stern, H.S. and Rubin, D.B. (1995). Bayesian Data Analysis, Chapman & Hall: London. [13] Huggins, R.M. & Loesch, D.Z. (1998) On the analysis of mixed longitudinal growth data. Biometrics [14] Huggins, R.M., Loesch, D.Z., & Sherman, S.L. (1998) A branching nonlinear autoregressive model for the transmission of the fragile X dynamic repeat mutation. Ann. Hum. Genet. 62 337-347. [15] Huggins, R.M. & Basawa, I.V. (1999) Extensions of the bifurcating autoregressive model for cell lineage studies. J.Appl.Prob. 36 1225-1233.
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[16] Morris, A., Morton, N.E., Collins, A., Macpherson, J., Nelson, D. and Sherman, S. (1995) An n-allele model for progressive amplification in the FMR1 locus. Proc. Natl. Acad. Sci. USA 92 4833-4837. [17] Morton, N.E. and Macpherson, J.N. (1992) Population genetics of the fragile X syndrome: multiallelic model for the FMR1 locus. Proc. Natl. Acad. Sci. USA 89 4215-4217. [18] Muirhead (1981).Aspects of multivariate statistical theory, John Wiley: New York. [19] Murray, M.A., Macpherson, J.N., Pound, M.C., Sharrock, A., Youings, S.A., Dennis, N.R., McKechnie, N., Lineham, P., Morton, N.E., Jacobs, P.A.(1997). The role of size, sequence and haplotype in the stability of FRAXA and FRAXE alleles during transmission. Hum. Mol. Genet. 6:173-84. [20] Park, Jeong-gun &; Basawa, I.V. (2000) Optimal estimating equations for mixed effects models with dependent observations. Technical report 2000-16, Department of Statistics, University of Georgia. [21] Robert, C.P. (1994) The Bayesian Choice. New York: Springer-Verlag [22] Robert, C.P. (1998). Discretization and MCMC Convergence Assessment, Springer-Verlag: New York. [23] Staudte, R.G., Zhang, J., Huggins, R.M. and Cowan, R. (1996). A reexamination of the cell lineage data of E. O. Powell. Biometrics., 52, 1214-1222.
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Appendices In the appendices we derive the joint and conditional densities required to estimate the model parameters using MCMC, and then give the MCMC algorithm.
A
Joint Densities
Using the notations introduced in the paper, it follows that the joint conditional density of g(Y) given Θ, 7 and the observed ancestor of each family is H
{g(Y)\θ,Ί}
P
Nh
nh=fhfk
ί>{5(Y)|ΘJQΠ Π h=lf=l nhf
H Nh
ΐ[p{9(Yhfki)\β,βh,βf\σ2,δ2F}
k=l 1=1
h=l /=1 k=l
{g(Yhfki)-Xhfk[β 2(PpIF(hfk)
+ σ*) (A.1)
The joint prior density of the parameter Θ given 7 is H Nh
π(θ|7)
H
Σ
Π Π Wrl /o) Π W Λ o ) h=lf=l
h=l
H Nh /ι=l/=l H X h=l
{
1
ff
Λ=l/=1
200
HUGGINS, QIAN AND LOESCH
x|Σ Λ 0 Γ* / 2 exp {-^ x|ΣoΓ 1/2 exp {—tr&^iβ
- βo)(β - βoΫ}]
(A.2) The joint prior density of the hyper-parameter 7 is τr(7)
= ω/0(Σ;o|ξ/θιΛ/o) ωω(Σ!fto|ξfco,ΛAθ) ^o(Σo|ξo,i?o) • bo{βo\b,Σ)
x(2π)-"/ 2 |ΣΓ 1 / 2 exp{-i(ft,-6)'Σ- 1 (A-6)}
(A.3)
where Γ m ( ) is the multivariate gamma function (see Muirhead 1981, pp. 61-63). In the simulations, the value of b was taken to be the estimate of β in the spline regression model g(Yhfki) = Xhfkβ We also used the following values in the simulation in such a way that they should have very weak effects on the simulation results: v = λ = up = \ F = 10,= Σ = RQ = Rho — Rfo — 10^10 with Jio being the 10 x 10 identity matrix, and £o = 6ιθ = ζfo = 50.
B
Posterior Conditional Densities
In order to simulate the posterior distributions using MCMC methods we need a number of posterior conditional densities. The joint posterior density of Θ, 7 given the observed ancestor of each family is
The conditional posterior density of θ given 7 and the observed ancestor of each family is p{g(Y)|Θ,γ}7r(Θ|Ύ)
fR
.
201
RANDOM COEFFICIENT MODELS
The conditional posterior density of 7 given Θ and the observed ancestor of each family is
C
Simulating the Posterior Densities by MCMC
To simulate the posterior distributions of the β^s and βί s, we first generate a random sample for (©,7) from the posterior density π(θ,7|Y). Then we extract those values of βh and βf in the sample, which clearly comprises a 1 random sample from the posterior distributions of (/?£, βj) . So the question is how to generate a random sample from the posterior density π(θ,7|Y). To answer this question we apply an Markov chain Monte Carlo method (MCMC) which uses a Metropolis-Hastings acceptance-rejection algorithm alternately to the two blocks of the random quantity (©,7). In other word, this is the so-called MCMC block-at-a-time algorithm (refer to Chib and Greenberg, 1995). We list the algorithm in the following: Obtain the initial values (7(0), 1. Generate a matrix 7^°) from the prior π(7). 2. Generate a vector θ<°) from the prior 7r(e Update ( 7 ϋ), θ ^ ) to {^j+ι\ θ ^ + 1 ) ) . Repeat for j = 0,1,
, N - 1.
1. Use an M-H acceptance-rejection algorithm to generate a matrix 7^ + 1 ) from the conditional posterior density π ( 7 | Y , θ ^ ) : - Generate an initial matrix 70 from τr(7). - Repeat for i = 0,1, , / — 1. - Generate a matrix 7' from π(7) and u from the uniform distribution ZY(/, 00). - If u < Oij(ji ,V), set 7^\ = 7 ; . The acceptance probability is defined by
a 7(7ί ( τ ω τ7 V mini )
' ~
π ( θ | 7 )
U(Θ(%?Y
l
- Finally set 2. U s e a n M - H a c c e p t a n c e - r e j e c t i o n a l g o r i t h m t o g e n e r a t e a v e c t o r QU+ι) f r o m t h e c o n d i t i o n a l p o s t e r i o r d e n s i t y π ( ^ ^
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HUGGINS, QIAN AND LOESCH
- Generate an initial vector ΘQ fr°m 7r(θ|7^ + 1 )). - Repeat for q = 0,1, , Q — 1. - Generate a matrix θ ' from π(θ|7^ + 1 ^) and u from the uniform distribution Z//(/, oo). - If u < OLQ(QΨ,&), bility is defined by
set θ ^ i = ©'. The acceptance proba-
- If u > aθ(θφ,&), set Θ% = θ[j). - Finally set θ^ + 1 ) = θ § } . Return the sequence {(7<°\ β ^ ) , ( 7 ( 1 ) , θ W ) , • • •, (7 ( Λ Γ ) , Θ(JV))}. As in any MCMC method, the sequence generated by the above algorithm is actually a Markov chain with τr(θ,7|Y) a s i*s invariance density. So by ignoring the first iVo values the sequence can be approximately regarded as a random sample from the posterior density τr(θ, 7|Y), provided that both NQ and N are sufficiently large. In our simulations we found that when taking / = Q = 50 the simulated Markov chain became convergent after No > 48 runs.
205
Institute of Mathematical Statistics LECTURE NOTES — MONOGRAPH SERIES
SEMIPARAMETRIC INFERENCE FOR SYNCHRONIZATION OF POPULATION CYCLES RE. Greenwood Dept. of Mathematics, Arizona State University, Tempe, Arizona and Dept. of Mathematics, University of British Columbia, Canada D.T. Haydon Centre for Tropical Veterinary Medicine Easter Bush, Roslin, Midlothian, U.K.
1
Introduction
We consider a dynamic random field. On each of a discrete array of sites is located a hyperbolic dynamical system perturbed by noise. We assume that the dynamics are identical, with a unimodal limit cycle and that the perturbations are independent, centered, and with the same distribution. In addition the individual processes are coupled with one another in a homogeneous pattern. The coupling may be global, in which case we are thinking of a mean-field type of system. Or the coupling may be local, the coupling strength between each site and its neighbors attenuating with distance. The application we have in mind is to cycling populations of animals, where the log of each local population increases roughly linearly to an apparent critical point from which it falls precipitously to a minimum. The data is discrete in space and time, being based on periodic reports from catchment or reporting regions. In a previous study [1] we focussed on data from Canadian lynx populations. Lynx population cycles are known to follow those of snowshoe hare. Previous analyses of this data have been concerned with inferring the length and regularity of the evident population cycles. We consider in [1] the very different challenge of estimating a parameter identified as strength of coupling among populations. That paper is primarily addressed to data analysis and interpretation. The emphasis in this report is on the steps involved in arriving at a suitable model and estimator. We explore some of the difficulties posed by this rather unusual problem. In forthcoming studies we, with colleagues, will apply the method described here to cycling population data from Canadian muskrat and mink, and from the greysided vole of Hokkaido.
206
2
GREENWOOD AND HAYDON
Development of a Coupled Evolving Phase Field Model
To begin, let us introduce a general definition of synchronization applicable to random fields. Let X = {Xa,i € I,t = 0,1,2,...} denote the values at site i and time t of a dynamic random field. Let S = {£(•)*, t > 0} denote a real-valued functional or collection of functionals of {Xis, i € / , s < *}. Note that we allow S evaluated at time t to depend on data up to and including time t. Define S'-synchronization to mean {SX)t = 0, almost surely, for t in some time-set T. This gives us a flexible definition of exact synchronization. But a random field will not be exactly synchronized. In order to formulate a statistically useful definition we need to allow for and to measure departures from synchronization. For example, we probably want the mean and variance of S applied to random data to be small. We are led to the following: Definition. A dynamic random field X departs from 5-synchronization by no more than e over the time interval T if E(SX)Ί < e for all t eT. One might use other norms, e.g. Lι or Kullbach-Leibler instead of L 2 . However this definition has a familiar form and is computationally convenient. At each site i in an array of sites / is located a "skeleton" process which, in the absence of any noise or coupling can be written -ΪM+i = HXith
i e /, t = 0,1,2,....
(2.1)
In this treatment we write the dynamics as of first order in discrete time. We assume there is a unimodal limit cycle t(t),t = 0, . . . , p , ^(0) = t{p), where, since / is the same for each i, the form of the cycle, ί^ and its period, p, are the same for each site i. For definiteness let ^(0) be the minimum point of the unimodal cycle. If we picture the deterministic field (1) running in equilibrium, we see the periodic cycle ί{ ) being executed at each site, the only difference between sites being the phase, which will differ if the initial points X^o were not identical. Now suppose we watch, instead, the stochastic field, X^t+ι=f(Xit)
+ eiu
t 6 / , t = 0,l,2,...
(2.2)
where en represents a small, identically distributed, centered noise. A theorem of deterministic dynamics called the "shadowing lemma" implies that the stochastic paths of (2) shadow the paths of (1), where "shadow" means that they remain in a distributional neighborhood of the deterministic path up to a time shift. The differences among the paths at the various sites, then, in addition to the small width of this neighborhood, are the phases, which change in a random way. The neighborhood width depends on the
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INFERENCE FOR SYNCHRONIZATION
noise variance. This picture motivates a model for coupling based on the randomly evolving phases of the components. We now move our attention from the evolving random field of population levels, (2), to a corresponding evolving random field of phases. Going back to the deterministic model (1) we can unambiguously define the phase φa at site 2, time £, to be the time fraction of the current cycle, ^(0),... ,^(p), which has been accomplished at time t. Then each phase φu is in the interval [0,1). The arithmetic for phases is modi. We think of the set of points {Φit,i G /} as a set on the circle of circumference 1. As time advances the points progress around the circle. Since in fact we wish to consider the phase field associated with the stochastic field (2), where the "limit cycle" is a stochastic perturbation of the deterministic one, we may not see a unique minimum for each cycle, and the definition of φu may be ambiguous. We will assume that the noise en is small enough so that the ambiguity can be resolved by a device described in the next section. For the moment let us ignore this problem and assume that in the stochastic model the phase φn is defined as the fraction of the current orbit which has been traversed at time t by each path X{ of the stochastic field (2). We describe the structure of the phase field φa, i G /, t = 0,1,2,..., by writing Φiί+\ = Φit + 9it + tit
mod 1,
(2.3)
where gu is the fraction of the current orbit traversed at site i at time t. Now we introduce a hypothetical coupling force into the phase field which will shift the phase at each site i and time t in the direction of the "mean phase". For this purpose we need to devise an appropriate definition of mean for a set of random points on a circle. As mentioned above we identify the phase values with points on a circle of circumference 1. Between points x,y on this circle, let Δ(x,y) denote the signed smallest arc measured counter-clockwise between them. Then Δ(x,y) is positive or negative according to whether x leads or lags y, and (x,y)|<0.5. For each set of phases φu with t fixed, let φt be a solution of ψt)=0.
(2.4)
Then φt is almost surely uniquely defined and can be interpreted as the mean phase at time t on the circle, or equivalently on [0,1) mod 1. To model phase coupling among sites i in the array /, we insert a coupling term in expression (3) which moves the phases at time t + 1 in the direction of the mean phase at time t, and write Φi,t+i = Φit + 9it ~ cA{φiu φt) + eit mod 1,
i e /, ί = 0,1,....
(2.5)
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GREENWOOD AND HAYDON
The coupling strength c can take values in [0,1). Expression (5) says that in each time step, from t to t + 1, three changes occur in the phase at each site: (a) it advances according to phase dynamic ga inherited from the limit cycle of the "skeleton" process (1), (b) it is shifted in the direction of the mean of the phases as defined by (4) by a proportion c of its distance from this mean, and (c) it is perturbed by a centered random effect. About the en we assume only that for each t they are conditionally independent given the past of the process {φu}, with the same conditional distribution for each i and t. In order to simplify our computations we would like to omit the modi in relation (5). This is possible if it does not happen, or happens only rarely, that the combined effect of (a), (b), and (c) at a particular timestep t is large enough that the phase increment at a single step exceeds 1. In the model we make this assumption. If it is occasionally violated in the data we make an appropriate adjustment. Assuming, then, that the noise is sufficiently small relative to the coupling, (5) can be written as +i,^+1)
= (1 - c)Δ(φiuφt)
+ eit + {git - φt+i + Φt),
<2 ^
The last grouped term in (6) has mean 0 as can be seen from considerations of symmetry. In addition, for each t the various values in i are conditionally independent given the past of the phase field. We have assumed that the noise increments en are small and centered and conditionally independent given the past of the phase field. Without altering this assumption we can regard the last grouped term in (6) as part of the noise and write (6) as Δ(&, t + i, φt+ι) = (1 - c)A{φiu φt) + ηiu
i E /, t = 0,1,....
(2.7)
Relation (7) describes a stochastic process of ARl-type. It differs from the usual AR1 model in that the process is a vector-valued function of a distinct vector process. The underlying process has vectors of phases as its values, whereas the process defined by (7) has values which are vectors of differences of these phases from the evolving central phase. Nevertheless the least squares type estimator is consistent for (1 — c) and that is what we used in [1]. One needs to know that there is a stationary law for the process defined by (7). This can be shown by an argument along the lines of arguments in Meyn and Tweedie's book [2], The fact that the state space is bounded simplifies the situation.
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INFERENCE FOR SYNCHRONIZATION
If we wish to model local rather than global coupling, then the central phase as seen from site i should be computed from the phases at sites near i. We then define the local centre of phases at i, to be the almost surely unique phase φit which is the solution of
i e J, t = 0 , 1 , . . . ,
(2.8)
3
where the numbers α^ are weights reflecting the fraction of the total coupling at site i to be attributed to interaction between sites i and j , Σ aij — 1. We _
_
3
arrive at a version of (7) with φit replacing φt in each equation. If edge effects are disregarded, and if α^ depends only on i — j , the system remains spatially homogeneous in law. In any case, a stationary distribution exists for the process and the least-squares-type estimator is consistent for 1 — c. Let us return to the notion of departure from 5-synchronization by no more that e, as defined early in this section. Perfect synchronization corresponds to departure zero, and higher levels of departure correspond to less synchronization. The synchronization measure we choose here is the meansquare deviation of the phase field from its mean φt, or φit, as defined by (4) or (8),
The departure from synchronization, then, is defined as
E{SX)2t = ±-ΣEA(φiuφt)2.
3
(2.10)
Estimation
In an initial application of the model presented here [1], we study synchronization in the well-known Canadian lynx data sets. Here we summarize a few of the results and refer to [1] for the full treatment and references. The first data set was compiled by Elton and Nicholson, in 1942, [4] spans the years 1821 to 1891 and is organized over six trading regions of the Hudson's Bay Company. The second data set, compiled by Statistics Canada, [5] is organized over eight Canadian provinces and territories and 2 spans the years 1919-1990. We used estimators of (1 - c) and σ where η is the noise increment in (7), which are analogous to well-known linear estimators for parameters of AR1 time series. The data analysis involves two difficulties peculiar to the phase-coupled model (7). As mentioned earlier it was not possible to identify uniquely
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the time points where minima of cycles occur in the data. Our treatment in [1] involves identifying the sets of possible minima and repeating the estimation procedure many times using random choices from these sets. We are exploring other possible ways to handle this problem in other data sets. A second difficulty involves discontinuities in the function A(φu,φt) at ±0.5, and a very few instances where A(φt+1^φt) < 0. Our handling of these is detailed in [1]. We mention these problems here to indicate the novel difficulties posed by data analysis in this context. The estimators we use for θ — 1 — c and for σ% are
θ = ϊ=i-ί=i n
i=\
i\ — l
_
2^ i\{φit,Φty t=l
(3.1)
/n(iV - 1) - 2. We can distinguish by looking at the residuals from these estimates the times at which synchrony is maintained by intermittent synchronizing events from the time periods of constant phase-coupling dynamics as expressed in expression (7). At the times of synchronizing events we see outliers in the residuals, whereas corresponding to periods of consistent coupling, data is clustered around the regression line. Times, thus detected, of synchronizing events correspond to times of decrease of the estimator (9) of asynchrony. The coupling estimates we obtained were c ~ 0.054 for the earlier data set and c ~ 0.011 for the later one. With local weighting the estimate doubled to c ~ 0.096 for the earlier data set and remained about the same at c ~ 0.005 for the later data set. The numbers for the earlier data set are significant according to tests using the estimated variances, and are significantly greater than estimates produced from simulated cycles with randomized phases from a model fitted to this data. Thus, although the estimates c from the lynx data seem small, we believe that they measure the phenomenon of coupling as intended. An alternative statistical approach to the study of synchronization of population cycles uses the correlation structure of the logged abundance data as in e.g. Jolliffe [3]. With this method, amplitude variability may confound the detection of synchronization. Further, since phase coupling is not modelled, correlational methods measure phase coupling only very indirectly.
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211
Acknowledgements This work was supported by NSERC Canada and the Crisis Points Group of the Peter Wall Institute of Advanced Studies at U.B.C. The second author acknowledges support from the Wellcome Trust.
References [1] Haydon, D.T. and Greenwood, P.E. (2000). Spatial coupling in cyclic population dynamics: models and data. Theoretical Population Biology, 58, 239-254. [2] Meyn, S.P. and Tweedie, R.L. (1993). Markov Chains and Stochastic Stability. Springer, Heidelberg. [3] Jolliffe, I.T. (1986). Principal Components Analysis. Springer, New York. [4] Elton, C. and Nicholson, M. (1942). The ten-year cycle in numbers of lynx in Canada. J. Anim. EcoL, 11, 215-244. [5] Statistics Canada. 1921-1990. Catalogue 23-207, Fur Production, Ottawa, Canada.
213
Institute of Mathematical Statistics LECTURE NOTES — MONOGRAPH SERIES
PLUG-IN ESTIMATORS IN SEMIPARAMETRIC STOCHASTIC PROCESS MODELS Ursula U. Muller Universitat Bremen Anton Schick * Binghamton University Wolfgang Wefelmeyer Universitat Siegen Abstract Consider a locally asymptotically normal semiparametric model with a real parameter ϋ and a possibly infinite-dimensional parameter F. We are interested in estimating a real-valued functional a(F). If ά# estimates a(F) for known $, and ϋ estimates #, then the plug-in estimator ά^ estimates a(F) if ϋ is unknown. We show that ά^ is asymptotically linear and regular if ά# and $ are, and calculate the influence function and the asymptotic variance of ά^. If a(F) can be estimated adaptively with respect to #, then ά^ is efficient if ά# is efficient. If a(F) cannot be estimated adaptively, then for ά^ to be efficient, ΰ must also be efficient. We illustrate the results with stochastic process models, in particular with time series models, and discuss extensions of the results. Key Words: Empirical estimator, asymptotically linear estimator, influence function, regular estimator, Markov chain model, nonlinear regression, residual distribution, nonlinear autoregression, innovation distribution, stochastic equicontinuity, stochastic differentiability.
1
Introduction
Let Vn = {PnϋF : ^ G Θ,F G 7 } denote a sequence of semiparametric models, with θ one-dimensional and T a possibly infinite-dimensional set. We are interested in estimating a real-valued functional a(F). For each ϋ Research partially supported by NSF Grant DMS 0072174
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MULLER, SCHICK AND WEFELMEYER
let ά# be an estimator for a(F) when ΰ is known, and let ΰ be an estimator for #. The plug-in estimator for a(F) is ά^, obtained by substituting ΰ for ΰ in ά#. In Section 2 we introduce a semiparametric version of local asymptotic normality, and a concept of asymptotically linear estimators for functionals on such models. This concept requires embedding the semiparametric model into a "nonparametric" supermodel which is to some extent arbitrary, although for specific types of stochastic models there usually is a natural choice. We recall two results which are essentially known, at least for i.i.d. models and Markov chain models. The first characterizes regular estimators among asymptotically linear ones; the second characterizes efficient estimators. In Section 3 we show that ά^ is asymptotically linear if ά# and ϋ are, and calculate the influence function of ά^. In Section 4 we assume that both ά# and ϋ are asymptotically linear and regular, and show that then ά^ is also regular. The characterization of regular estimators then allows comparison of the asymptotic variance of the plug-in estimator with the minimal asymptotic variance. In particular, if a(F) can in principle be estimated adaptively with respect to #, i.e., if knowledge of ΰ does not contain information about a(F)j then ά^ is efficient whenever ά# is efficient for known ϋ. lΐa(F) cannot be estimated adaptively with respect to #, then both ά# and ΰ must be efficient for ά^ to be efficient. For i.i.d. observations and estimators of the form ά# = a(F$), these results are due to Klaassen and Putter (1999). Sections 5 and 6 contain applications to models with i.i.d. observations and to Markov chain models, respectively. The discussion is heuristic in these two sections. Some extensions of the results are outlined in Section 7.
2
Characterizing Regular and Efficient Estimators
In this section we recall briefly characterizations of regular and of efficient estimators of real-valued functional in semiparametric models. For the i.i.d. case we refer to Bickel, Klaassen, Ritov and Wellner (1998), Chapter 3 and in particular Section 3.4. For Markov chains see Wefelmeyer (1999); for general models and counting process models see Andersen, Borgan, Gill and Keiding (1993, Chapter VIII); for general parametric models see Le Cam and Yang (1990). We will embed the semiparametric model in a "nonparametric" supermodel. The reason is that we want a sufficiently rich class of "asymptotically linear" estimators, and asymptotic linearity will be defined in terms of statistics approximating local likelihood ratios; see below. For n G N let Vn denote a collection of probability measures on some
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PLUG-IN ESTIMATORS
measurable space (Ωn, Tn). Fix a sequence Pn in Vn and assume that the model is locally asymptotically normal at Pn in the following sense. There f is a linear space H with inner product (h,h ) and corresponding norm ||/ι||, there is a sequence of random linear functionals Sn on H, and for each h E H there are perturbations Pnh of Pn within Vn such that (2.1)
\\h\\ + oPn{l), under P n ,
(2.2)
with N denoting a standard normal random variable. The linear space H may be interpreted as (approximate) tangent space oίVn at Pn. Now consider a sequence of semiparametric submodels Vn — {PnϋF '• ^ G Θ J F G ^ } o f ? n , with θ one-dimensional and T an arbitrary, possibly infinite-dimensional set. We fix ΰ and F and consider perturbations ϋnu = ϋ + n~1/2u of ϋ and Fnυ of F, with v in some linear space V. In general, the appropriate rate may be different from n" 1 / 2 , but it will be n" 1 / 2 in our applications, which is why we have taken it to be n~ιl2 here. We assume that (2.1) and (2.2) hold at Pn = P n #F 5 and that the semiparametric model is locally asymptotically normal in the following sense. There are an element m in H and a linear operator D : V ->• H such that for Pnuυ = PnϋnuFnv * 7
log ^
= Sn(um + Dv) - I||um + Dt;|| 2 +
oPnϋF{l).
Prom (2.2), Sn(um + -Dv) => ||i4m + 2?v||JV
under Pn#F
The tangent space of the semiparametric model is H=[m] + DV, with [m] denoting the linear span of m. The one-dimensional space [m] is the tangent space for known F, obtained by perturbing ΰ. The space DV is the tangent space for known #, obtained by perturbing F. We assume that DV is closed, and that m does not belong to DV. We may think of m as the score function for ΰ. Let α(#, F) be a real-valued functional. It is called differentiable at (#, F) with gradient g Ίΐ g £ H and n 1 / 2 (α(τ? n ί z ,F n v ) - α(tf,F)) -> {g,um + Dv) for u G Λ, v € V.
(2.3)
The canonical gradient g is the projection of g onto if; it is therefore of the form ΰm + Dv.
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MULLER, SCHICK AND WEFELMEYER
An estimator ά is called asymptotically linear for α(#, F) with influence function bifbeH and 1 2
n / (ά-a(ϋ,F))
= Sn(b) + oPnΰF(l).
(2.4)
An estimator ά is called regular for α(#, F) with ZzYm£ L if L is a random variable such that ι/2
n (ά
- a(βnu, Fnv)) => L under P n m ; for all u G # , Ϊ; G V.
(2.5)
The convolution theorem of Hajek (1970) says that L = \\g\\N + M
in distribution,
with M independent of N. This justifies calling a regular estimator a efficient for a(ΰ,F) if it is asymptotically normal with variance ||ff||2, nιl2{a - α(0, F)) =• \\g\\N under P n i 9 F . We have the following two characterizations: (1) An asymptotically linear estimator is regular for α(i?,F) if and only if its influence function is a gradient of α(??,F). (2) A regular estimator is efficient for α(#, F) if and only if it is asymptotically linear with influence function equal to the canonical gradient of a(ΰ,F). Now it becomes clear why we have introduced the "nonparametric" model. If we restrict attention to the semiparametric model, then there is only one gradient, the canonical one, and all regular and asymptotically linear estimators are asymptotically equivalent. In the examples of Sections 5 and 6 we will need to consider estimators whose influence functions are non-canonical gradients. The concept of asymptotically linear estimators is arbitrary in that it depends on the choice of "nonparametric" model; see Wefelmeyer (1991).
3
Asymptotic Linearity of Plug-in Estimators
Consider the problem of estimating a real-valued functional a(F) in the semiparametric model Vn = {PnΰF '• ΰ Eθ,F G T}. Fix ϋ and F. Suppose that for each τ near ΰ we have an asymptotically linear estimator aT of α(F), with influence function 6T. We assume that asymptotic linearity holds locally uniformly in shrinking neighborhoods of 7?, sup |n1/2(ai?n]ί _ a(F)) - Sn(bκJ\
= o P n ,,(l),
(3.1)
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PLUG-IN ESTIMATORS and that Sn(bΰnu)
is stochastically differentiable at u = 0,
sup \Sn(bΰnJ
- Sn(b#) + (m,bϋ)u\ = oPnΰF(l).
(3.2)
Now let ϋ be asymptotically linear for ΰ, with influence function c,
By conditions (3.1) and (3.2), the plug-in estimator ά^ fulfills =
Sn(b^) +
=
Sn(bΰ -
oPnΰF(l) (m,b#)c)+oPnϋF(l).
This means that ά^ is asymptotically linear for a(F) with influence function (3.3)
b = b#-{m,bΰ)c
If (m, ) = 0, then we can relax the assumption that ϋ is asymptotically linear to n1/2-consistency and still get that the plug-in estimator is asymptotically linear, now with influence function 6 = . Asymptotic linearity (3.3) of the plug-in estimator also follows if we replace conditions (3.1) and (3.2) by a non-uniform version of (3.1), - a(F)) = Sn(b#) + o P n , F ( l ) ,
(3.4)
and an expansion of ά^,
n1/2(^ ~ &*) = - K bϋ)nι'2φ
-ΰ) + oPnΰF(1).
(3.5)
An application is Example 3 in Section 6. R e m a r k 1. (Plug-in and sample splitting.) Our requirements (3.1) and (3.2) are stronger than the following conditions. For every bounded sequence
Sn(b*nun) - Sn(b»)
=
Sn(bΰnun)
+ o P τ ι , F (l),
(3.6)
=
-un(mM
+ oPnΰF(l).
(3.7)
Property (3.7) appears quite frequently in the literature. It has been been verified by Drost, Klaassen and Werker (1997), Jeganathan (1995), Koul and Schick (1997) and Kreiss (1987) for some time series models. A simple sufficient condition for (3.7) is given in Schick (2000) in the context of i.i.d. observations.
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MULLER, SCHICK AND WEFELMEYER
It was shown by Klaassen and Putter (1999) in the context of i.i.d. observations that under these weaker conditions one can use sample splitting techniques to construct a modified version of the plug-in estimator with influence function b as in (3.3). Their construction can be generalized to stationary and ergodic Markov chains using the sample splitting techniques developed in Schick (2001). But this will not be pursued here. Remark 2. (Stochastic differentiability.) We will check stochastic differentiability (3.2) for specific types of processes in Sections 5 and 6, using stochastic equicontinuity of empirical processes. Here we indicate that (3.2) also follows from a locally uniform version of local asymptotic normality. Compare the proof of Theorem 6.2 in Bickel (1982). Since F is fixed in (3.2), we will omit it from the notation. Fix ϋ and set τ = ϋnu = ldΛ-n~ι'2u. Assume that the parametric family {Pn<β : ΰ G Θ} is locally asymptotically normal at #, log - ^
= uSnΰ(m)
- -u2\\m\\l +
oPnΰ(l).
Assume also that for τ near ϋ there is a tangent space Hτ such that for each bτ £ Hτ we have local asymptotic normality at r, l o g % ^ = Snτ(bτ) - hbT\\2T +
oPnr(l).
Then 1 2
2
1
2
2
2
If bτ is continuous at r = ΰ in an appropriate sense, PUτbτ will be approximately equal to Pnϋ,um+bϋ (For a more explicit argument it would be convenient if the sequence of "nonparametric" supermodels Vn were indexed by an infinite-dimensional parameter; see LeCam (1986, Chapter 11) and Greenwood and Wefelmeyer (1991, Section 4).) Hence log dPnτbg
dPnΰ
=
log- dpn*,™+*>*
=
Sn4um + bΰ)--\\um + bΰ\\l + oPnϋ(l).
°g
dPnϋ
(3.9)
If both Snτ and || | | τ are continuous at r = ϋ in an appropriate sense, we obtain from (3.8) and (3.9): = o P n i 9 (l). Stochastic differentiability (3.2) requires that the supremum over |ιt| < Δ is stochastically negligible. For this, we need a corresponding strong version of local asymptotic normality, as introduced in Fabian and Hannan (1985, Section 9.1).
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PLUG-IN ESTIMATORS
4
Efficient and Adaptive Plug-in Estimators
We continue the discussion of plug-in estimators under additional assumptions. As in Section 3, let a(F) be a real-valued functional of F. Fix # and F. For r near ϋ let άτ be a locally uniformly asymptotically linear estimator of a(F) in the sense of (3.1), and let ΰ be an asymptotically linear estimator of ΰ. Now assume, in addition, that a(F) is differentiate (2.3) at (ΰ,F), that ά# is regular at (#,F) for known ΰ, and that ϋ is regular at (ΰ,F). Then we can decompose the canonical gradient of a(F) and the influence function of the plug-in estimator ά^ as follows. Let cp denote the canonical gradient of ϋ when F is known. It is of the form CF = tm with t determined by -ΰ) = u = {tm, um), i.e., t = ||m||~ 2 and cF = \\m\\~2m. The squared length ||m|| 2 of m may be called the Fisher information for ϋ when F is known. Let Dvm be the projection of m onto DV. When ϋ is unknown, the canonical gradient of ϋ is characterized by three properties. It is in H = [m] + DV, orthogonal to DV, and its projection onto [m] is cp Hence it is of the form c = t(m — Dvm) , with t determined by (c — ϋp,m) = 0, i.e., t = (m — Dvm, m)~ι = ||m — Dvm\\~2. Hence the canonical gradient of ΰ is c=\\m-Dvm\\-2(m-Dvm). The squared length \\m — Dvm\\2 of m — Dvm is the Fisher information for ΰ. Let g# denote the canonical gradient of a(F) when ϋ is known. The canonical gradient ~g of a(F) for unknown ΰ is characterized by three properties. It is in H — [m] + DV, orthogonal to m, and its projection onto DV is gϋ. Hence g — g# is of the form tc, with t determined by (m,p) = 0, i.e., t = -(m,g#), i.e., g = gΰ-{m,g#)c.
(4.1)
Since ϋ is regular for ϋ, we obtain from characterization (1) of Section 2 that the influence function of ϋ is a gradient of ΰ, say c. Hence (4.2) Since ά# is regular for a(F) when ϋ is known, we obtain from characterization (1) of Section 2 that the influence function of ά# is a gradient of a(F) for known ΰ, say g#. Hence (4.3)
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MULLER, SCHICK AND WEFELMEYER
From (3.3) we obtain that the plug-in estimator ά^ is asymptotically linear for a(F), with influence function (4.4)
9 = 9ΰ -(m,g#)c. Prom (4.1) and (4.4) we obtain 9 -9" = 9ΰ -9# - (m,g# - g#)c - {m,gϋ)(c - c).
(4.5)
It follows from (ra, c) = 1 and relations (4.2) and (4.3) that g-g is orthogonal to Ή. Hence g is a gradient. Characterization (1) of Section 2 now implies that the plug-in estimator ά^ is regular. Since g — g and c — c are orthogonal to if, the asymptotic variance of the plug-in estimator ά^ is -\\m - Dυm\\-2{m,gΰ
- gΰ)2 - 2(c - c,gϋ - S#)(m,3#
If ά# is efficient for a(F) when i? is known, and ΰ is efficient for i?, then 9ΰ — 3i9 a n d c = c. Hence g — ~g by (4.5), and the plug-in estimator ά^ is efficient for a(F). By (4.1), its asymptotic variance is
llsll2 = ll^ll2 + \\m - Dvm\\-2(m,gϋ)2.
(4.7)
If ά^ is efficient for a(F) when ΰ is known, then by (4.5) the influence function of the plug-in estimator ά^ is g = g-(m,gΰ){c-c),
(4.8)
and by (4.6) the asymptotic variance of α^ is 2
2
2
(4.9)
If ϋ is efficient for #, then by (4.5) the influence function of the plug-in estimator ά^ is 9 = 9 + 9ϋ -9ϋ ~ {™>,9ϋ ~ g#)c,
(4.10)
and by (4.6) the asymptotic variance of ά^ is
llίll2 + \\g* - VoW2 ~ \\m - Dvm\\-2(m,gϋ - gϋf.
(4.11)
We say that a(F) can be estimated adaptively with respect to ΰ if the asymptotic variance bound for a(F) is not decreased by knowing ΰ. This is the case if and only if Ίj = ~gϋ. By (4.1), this is equivalent to ( m , ^ ) = 0. Then ~g does not depend on c. Hence the plug-in estimator ά$ is efficient whenever ά# is efficient for known #, and the asymptotic variance is ||g#|| 2 . We say that F can be estimated adaptively with respect to ϋ if for every differentiable functional a(F) the asymptotic variance bound for a(F) is not decreased by knowing ΰ. This is equivalent to orthogonality of m and DV. Then ϋ can also be estimated adaptively with respect to F , and c = cp = 2
221
PLUG-IN ESTIMATORS
5
The i.i.d. Case
If we have i.i.d. observations ΛΊ,... ,X n , then a natural candidate for the "nonparametric" model of Section 2 is the usual nonparametric model, with completely unknown distribution Q(dx) of X{. (Larger nonparametric models are obtained by allowing the observations to be dependent.) Fix Q. Set Qh = J h(x)Q{dx) and H = L2fl(Q) = {he L2(Q) : Qh = 0}. For h E H set The approximation is meant in the sense of Hellinger differentiability. The joint law of X L , . . . , Xn is Pn = Qn. We have local asymptotic normality:
(Qhψ2N, with N standard normal. This is (2.1) and (2.2) with
V
,
(h,ti) = Q(hti).
Remark 3. (Stochastic differentiability.) In the stochastic differentiability condition (3.2), the parameter F is fixed, and we may omit it. Let {Q$ : ϋ G Θ} be a parametric family of distributions of X{. For r near ϋ let bτ G ^2,o(Qr) Stochastic differentiability (3.2) follows if bτ is differentiate at r = ϋ in an appropriate sense. By Taylor expansion, sup
H<Δ'
=*P»«U)
From QT6T = 0 we obtain by taking the derivative under the integral, (5.2) with nriΰ = dτ=#dQτ/dQΰ the score function for ϋ. Relations (5.1) and (5.2) imply stochastic differentiability (3.2). A proof for fixed bounded sequences u = un is in Schick (2000). For (5.2) it is essential that Qτbτ = 0, in other words, that bτ is in the nonparametric tangent space, i.e., that bτ(Xi) is a statistic which approximates a local likelihood. n -i/2 γj}=ι
222
MULLER, SCHICK AND
WEFELMEYER
For stochastic differentiability (3.2) to hold, the function b# need not be differentiable. For r near ϋ consider the empirical process
If the collection of functions 6 r , r near #, fulfills an appropriate bracketing condition, then vnτ is stochastically equicontinuous at r = ϋ\ For each ε, η > 0 there is δ > 0 such that limsupP n #( sup
< ε.
\vnτ -vnϋ\>η)
Such a result was first proved by Daniels (1961) and Huber (1967) to obtain asymptotic normality of the maximum likelihood estimator under weak conditions on the score function; for a general version see Pollard (1985). For T = ΰnu we obtain sup =
OPn
,(l).
(5.3)
From QTbT = 0 we obtain
= Qΰbτ-Qτbτ
= ~(τ (5.4)
Relations (5.3) and (5.4) imply stochastic differentiability (3.2). Example 1. (Nonlinear regression.) Let (Xi, YΊ),..., (X n , Yn) be pairs of real observations with The εi are i.i.d. with density f(y) which has mean zero and finite variance but is unknown otherwise. The X{ are independent and independent of the Si and have unknown distribution function G(y). The pair (Xi,Yi) plays the role of Xι in the general setting. The model is semiparametric. The distribution of (Xi, Yι) is
Q»fG(dx,dy)
= dG{x)f(y - r(β,x))dy.
Fix 7?, / and G. We introduce perturbations
fnz(y) dGnw{x)
= =
ι 2
dG{x){\+n- l w(x)).
223
PLUG-IN ESTIMATORS
The density fnz must integrate to one and have mean zero, so z runs through
Z = {zβ L2(f) : Jz(y)f(y)dy = 0, J yz(y)f(y)dy = 0}. The function Gnw must be a distribution function, so w runs through L2fl{G) = {we L2(G) : j w{x)dG(x) = 0}. The perturbed distribution of (X^Yi) is dx d
Qnuzw(dx,dy) = Q#nufnzGnw( i y) 12
= QϋfG{dx, dy) (l + n- '
= dGnw{x)fnz{y
-
r(ϋnu,x))dy
(ur(0, x)i{y - r(0, *))
where r(ϋ,x) is the derivative of r(ΰ,x) with respect to #, and ^(y) = —f'{y)lf{y) is the score function for location of the error distribution. Hence the tangent space H of the nonlinear regression model consists of functions h{x, y) = ur(ϋ, x)i(y - r(tf, x)) + z(y - r(tf, x)) + tι (a ). It is therefore of the form ~H = [m] + DV of Section 2, with V = Zx L2,o(G), m(z,y) = r(i9, x)^(y - r(tf, a:)),
Dv(a:, y) = z(y - r(ΰ, x)) + w(x).
Note that by taking the derivative under the integral,
E(ε£(ε)) = Ix£(x)f{x)dx = - ί xf'(x)dx = 1.
(5.5)
Note also that w(x) is orthogonal to both m(x, y) and z(y — r(ΰ, #)), so that both ϋ and / are adaptive with respect to G. We want to estimate the expectation
= Jk(y)f(y)dy of an /-square-integrable function k under the error distribution. The usual estimator is the empirical estimator based on the estimated errors,
n
with ii = Yi—r(ΰ, Xi). A natural estimator of?? is the least squares estimator i?, which solves
224
MULLER, SCHICK AND WEFELMEYER
The least squares estimator is asymptotically linear with influence function (Er(ϋ,X)2)-ιr(ΰ,x)(y-r(ϋ,x)).
c(x,y) =
We have (m,c) = Er{ϋ,X)2 by (5.5), and c J_ DV since Jyz(y)f{y)dy = 0 for z G Z. Hence c is a gradient of ΰ. The empirical estimator of a(f) = Ek(ε) based on true innovations is
Its influence function is
For v = (z,w) G Z x I/2,o(G) we have
n^WA.) - α(/)) -> £(*(φ(e)) = (», Dυ). Hence g$ is a gradient of α(/) when Ί9 is known. It fulfills
Hence by Remark 3, an appropriate bracketing condition on the collection of functions bτ(x,y) = k(y — TX) — Ek(ε) implies stochastic differentiability (3.2) of the form
sup M<Δ
Σ ι uEr(4,X)E(l(ε)k(ε))\=oPa,/G(l). i=
It follows from (3.3) that the plug-in estimator ά^ is asymptotically linear for a(f) with influence function 9
=
9ϋ-{m,gϋ)c
-
k(ε) -Ek(ε)
-Er(ΰ,X)E(ί(ε)k(ε))(Er(ΰ,X)2)-1r(ΰ,x)ε.
Efficient estimators for ΰ are constructed in Schick (1993). The canonical gradient ~g and an efficient estimator for Ek{ε) are in Mύller and Wefelmeyer (2000a).
225
PLUG-IN ESTIMATORS
6
Markov Chain Models
Let XQ, ..., Xn be observations from a homogeneous and uniformly ergodic Markov chain with transition distribution Q(x)dy) and invariant law π(dx). Assume for simplicity that the chain is stationary. The natural "nonparametric" model of Section 2 is described by the collection of all such transition distributions. Fix Q. Set Qxh = f Q(x,dy)h(x,y) and H = {he L2(π ® Q) : Qxh = 0}. For h e H set Qnh(x,dy) = Q(x,dy)(l + rΓ The approximation is meant in the sense of Hellinger differentiability for Markov chains. The joint law oϊ X$,... ,Xn is Pn{dx0, . ,dx n ) = π(dxo)Q{xo,dx\)
Q(xn-Udxn).
We have local asymptotic normality:
i = ι
with N standard normal. This is (2.1) and (2.2) with 1
2
Sn(h) = n" / Σ h{Xi-UXi),
(Λ, ti) = π ® Q(hti).
2=1
Remark 4. (Stochastic differentiability.) The arguments of Remark 3 translate to stochastic process models. Stochastic equicontinuity for Markov chains was obtained by Ogata (1980) in connection with asymptotic normality of maximum likelihood estimators. Results for general discrete-time stochastic processes are in Andrews (1994) and Andrews and Pollard (1994). Let {Q$ : ϋ G Θ} be a parametric family of transition distributions of X{. For r near ϋ let bτ be π r ® Qr-square-integrable with f Qr(x,dy)bT(y) = 0 for all x. The score function for ϋ is
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MΪJLLER, SCHICK AND WEFELMEYER
If the functions bτ fulfill an appropriate bracketing condition for r near #, we have stochastic differentiability (3.2) of the form sup H<Δ
Example 2. (Nonlinear autoregression.) The observations XQ, ... ,Xn are real with The ε; are i.i.d. with density f(x) which has mean zero and finite variance but is unknown otherwise. Conditions for uniform ergodicity are in Bhattacharya and Lee (1995) and An and Huang (1996). The model is semiparametric, with transition distribution (x, dy) = f(y - r(0, x))dy. Fix ϋ and /. We introduce perturbations ϋnu fnv(x)
= ϋ + n-ι'2u, = f(x){l +
n-ι'2v{x)).
As in the regression example, Example 1, the function v runs through V = {υ e L2(f) : ίv{x)f(x)dx = θjxv(x)f(x)dx
= 0}.
The perturbed transition distribution is = fnυ(y x, dy) (l + n-1'2(ur{ϋ,χ)l(y
-
r{ϋnu,x))dy
- r(0, x)) + υ(y - r(ΰ,
where r(ϋ,x) is the derivative of r(ϋ,x) with respect to ϋ, and i(x) = —f'(x)/f(x) is the score function for location of the innovation distribution. Hence the tangent space H of the nonlinear autoregressive model consists of functions h{x,y) = ur(ϋ, x)i(y - r(0, x)) + v{y - r(0, x)). It is therefore of the form H = [m] + DV of Section 2, with m(z, y) = r(ΰ, x)i(y - r(ΰ, x)),
Dυ(x, y) = v(y - r(#, x)).
227
PLUG-IN ESTIMATORS We want to estimate the expectation
= Jk(x)f(x)dx of an /-square-integrable function k under the innovation distribution. The usual estimator is the empirical estimator based on the estimated innovations,
ά= -n ] < with έi = Xi — r(ϋ,Xi-\). estimator #, which solves
A natural estimator of ΰ is the least squares
The least squares estimator is asymptotically linear with influence function
We have (ra,c) = Er(ΰ,X)2 by (5.5), and c J_ DV since Jxv(x)f(x)dx = 0 for v € V. Hence c is a gradient of ΰ. The empirical estimator of α(/) = Ek(ε) based on true innovations is 1^ Its influence function is
9ϋfa y) = k(y - ^ ) - Ek(ε). We have n 1/2 (α(/™) - α(/)) -> B(fc(e)t;(ε)) = (g*,Dv)
for t; G V.
Hence g$ is a gradient of a(f) when i9 is known. It fulfills " (m,gϋ) =
Er(ϋ,X)E(ί(e)k(ε)).
By Remark 4, an appropriate bracketing condition on the functions bτ(x, y) = k(y - rx) - Ek(ε) implies stochastic differentiability (6.1). It follows from (3.3) that the plug-in estimator ά^ is asymptotically linear for a(f) with influence function 9
= gϋ-{rn,g$)c = jfc(ε) - Ek{ε) -
Er{ϋ,X)E{i{ε)k{ε))(Er{ΰ,X)2)-ιr{ϋ,x)ε.
228
MULLER, SCHICK AND WEFELMEYER
Efficient estimators for ϋ are constructed in Drost, Klaassen and Werker (1997) and Koul and Schick (1997). The canonical gradient g and an efficient estimator for Ek(ε) is in Schick and Wefelmeyer (2000). Example 3. (Heteroscedastic linear autoregression.) The observations Xo5 , X n are real with
The Si are independent and, for simplicity, standard normal. Conditions for uniform ergodicity and efficient estimators for ϋ are in Maercker (1997) and Schick (1999). The model is semiparametric, with transition distribution 1
/υ — ϋx
where φ is the standard normal density. Fix ϋ and 5. Introduce perturbations tfmi = 0 + n~ 1 / 2 u, snυ{x) = s(x)(l + n-l'2v{x)). The function υ runs through V = ^ ( Z ) , where / is the stationary density. The perturbed transition distribution is Qnuv(x,dy) = QΰnuSnv{χ,dy) = Qϋs{x,dy)(l
= —-7-τy( y G
+ n-1/2{um{x,y)
T\
(
+ Dv(x,y))),
with
Since the normal distribution is symmetric, m and DV are orthogonal, and s can be estimated adaptively with respect to ΰ. Suppose we want to estimate the functional 2
a(s) = / s(x) dx. Jo For all u E R and v EV we have n1/2(a(snυ)
- a(s)) -> 2 / s(x)2v(x)dx = (Dva,Dυ + um) Jo 2 with va = l[ 0) i]S //. Hence a(s) is differentiate at (i?,s), with canonical gradient — ϋx\^
\
229
PLUG-IN ESTIMATORS Assume first that ΰ is known. Then we can estimate a(s) by l
/ h(x) Jo where
Here wn(x) = c~ιw(c~ιx), where w is a continuously differentiable symmetric density with compact support [—1,1], and cn is a bandwidth of order n " 1 / 3 . We show that a$ is asymptotically linear with influence function Dva. We do so under the assumption that 5 is twice continuously differentiable. Write (Xi - ΰXi^)2 = β(Xi-i) 2 (ε? - 1) + s(X - i ) 2 . Expand s(Xi_i) around s(x) to obtain , x Γ1A(x) aϋ - a(s) = / J o
+ 2s(x)8'{x)f1(x) j — fo{x)
2
dx
where A(X)
=
-
To . To
Λ
1=1
i=\
The assumptions imply that / is twice continuously differentiable. Hence we obtain uniformly for x G [0,1],
EA{x)2 = O(n-ιc-1) = O(n E(fo(x) - /(z)) 2 = 0{n-χc-1 + c4n) = O(n" 2 / 3 ), E(fι(x) - cnf'(x))2 = Oin-'c-1 + ci) = O(n- 2 / 3 ). We can also show that s u p o < x < i |/o(#) — / ( # ) | converges to zero in probability. From this and the facfthat / is bounded away from zero on [0,1], we can conclude that άΰ - a{s) = I -jγ^dx Now write
+ 0Pnΰs
(cn).
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MULLER, SCHICK AND WEFELMEYER
with I
n(y) = Jo
1
j^wn(y-x)dx.
It is easy to check that In converges in L,2(f) to the indicator of [0,1]. Combining the above lets us conclude that α# has influence function Dυa. 1 2 Suppose now that ϋ is unknown. Let ϋ be a n / -consistent estimator of ΰ. We prove that the plug-in estimator ά^ is efficient. We have already shown above that ά$ fulfills (3.4) with b$ = Dva. By the argument of Section 3, it remains to show (3.5). Since (m,Dva) = 0 by adaptivity, (3.5) reduces l 2 to asymptotic equivalence of ά^ and ά#, i.e., n / (a$ — ά#) = opnϋs(l). To prove this, we note first that
~ ^ / o fo(x) where B{x) = -Ys{Xi-ι): n ϊΞ{ Since / 0 B(x)/fo(x)dx converges to zero in probability, we obtain the desired result.
7
Extensions
1. We have assumed ϋ and a(F) to be one-dimensional. Extension to finitedimensional a(F) is straightforward; infinite-dimensional a(F) require additional technicalities. In nonlinear regression, Example 1, we may, e.g., be interested in estimating the error distribution function F, defined by F(t) — P(ε < t). For linear regression we refer to Klaassen and Putter (1999). Extension to finite-dimensional ϋ is also straightforward. We note that it may happen that a(F) is adaptive with respect to certain components of ί? only. For efficiency of ά^, efficient estimators are required only for the non-adaptive components of ΰ. Extensions of nonlinear regression, Example 1, are treated in Mύller and Wefelmeyer (2000a). Extensions of nonlinear autoregression, Example 2, are treated in Schick and Wefelmeyer (2000). 2. We have restricted attention to functionals a(F) of F only. The results may be extended to functionals α(i9, F) which depend also on ΰ. An interesting application is estimation of invariant distributions of time series, for example in linear autoregression Xι = ΰXi-ι + E{. Since Y^LxWej is distributed as the invariant law, we can write the expectation of a function k under the invariant law as j
Ek{X) = Ek(Σΰ εj)
= a(ΰ,F),
231
PLUG-IN ESTIMATORS
where F is the invariant distribution function. Hence Ek(X) can be estimated by a von Mises statistic or a [/-statistic based on estimated innovations; see Schick and Wefelmeyer (2001). 3. The results extend from semiparametric models {PnϋF : t f 6 θ , F E 7 J } to parametric families {Vn>β : ϋ G θ } of nonparametric models. This is of interest when we start from a nonparametric model Vn and impose a restriction which depends on an unknown parameter, say r#(Pn) = 0, leading to Vn* = {Pn r#(Pn) = 0}. For example, let XQ, . . . , Xn be observations from a Markov chain with transition distribution fulfilling /Q(x,dy)y = r{ϋ,x) for some ϋ. This is thenonlinear autoregressive model X{ = r($,Xi_i) + ε^, where the ε% are martingale increments, not i.i.d. as in Example 2. For estimators of ϋ see Wefelmeyer (1994), (1996), (1997a), (1997b); for estimators of the stationary law see Schick and Wefelmeyer (1999). The model may be written as a semiparametric model by introducing transition distributions F(x,dy) with / F(x, dy)y = 0 and writing Q{x,dy)=F{x,dy-r(ΰJx)). This is, however, technically inconvenient because we perturb ΰ and would need differentiability of F. Another example are i.i.d. observations (-XΊ, YΊ),..., ( I n , Yn) with joint law fulfilling the constraint E(a(X, Y, ΰ)\X) = 0, where α(X, Y, ϋ) is a given function. For plug-in estimators in such models see Mύller and Wefelmeyer (2000b). A special case is a{X,Y,ϋ) = Y - r(tf,X), i.e., Y{ = r(ϋ,Xi) + εu which differs from Example 1 in that we do not assume Z{ and X{ to be independent.
References Andersen, P. K., Borgan, 0., Gill, R. D. and Keiding, N. (1993). Statistical Models Based on Counting Processes. Springer Series in Statistics, Springer, Berlin. Andrews, D. W. K. (1994). Asymptotics for semiparametric econometric models via stochastic equicontinuity. Econometrica 62, 295-314. Andrews, D. W. K. and Pollard, D. (1994). An introduction to functional central limit theorems for dependent stochastic processes. Internat. Statist Rev. 62, 119-132. An, H. Z. and Huang, F. C. (1996). The geometrical ergodicity of nonlinear autoregressive models. Statist. Sinica 6, 943-956.
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Bhattacharya, R. and Lee, C. (1995). On geometric ergodicity of nonlinear autoregressive models. Statist. Probab. Lett. 22, 311-315. Bickel, P. J. (1982). On adaptive estimation. Ann. Statist. 10, 647-671. Bickel, P. J., Klaassen, C. A. J., Ritov, Y. and Wellner, J. A. (1998). Efficient and Adaptive Estimation for Semiparametric Models. Springer, New York. Daniels, H. E. (1961). The asymptotic efficiency of a maximum likelihood estimator. Proc. Fourth Berkeley Symp. Math. Statist. Probab. 1, 151163. Drost, F. C, Klaassen, C. A. J. and Werker, B. J. M. (1997). Adaptive estimation in time-series models. Ann: Statist. 25, 786-817. Greenwood, P. E. and Wefelmeyer, W. (1991). Efficient estimating equations for nonparametric filtered models. In: Statistical Inference in Stochastic Processes (N. U. Prabhu, I. V. Basawa, eds.), 107-141, Marcel Dekker, New York. Fabian, V. and Hannan, J. (1985). Introduction to Probability and Mathematical Statistics. Wiley, New York. Hajek, J. (1970). A characterization of limiting distributions of regular estimates. Z. Wahrsch. Verw. Gebiete 14, 323-330. Huber, P. J. (1967). The behavior of maximum likelihood estimates under nonstandard conditions. Proc. Fifth Berkeley Symp. Math. Statist. Probab. 1, 221-233. Jeganathan, P. (1995). Some aspects of asymptotic theory with applications to time series models. Econometric Theory 11, 818-887. Klaassen, C. A. J. and Putter, H. (1999). Efficient estimation of Banach parameters in semiparametric models. Technical Report, Department of Mathematics, University of Amsterdam. Koul, H. L. and Schick, A. (1997). Efficient estimation in nonlinear autoregressive time series models. Bernoulli 3, 247-277. Kreiss, J.-P. (1987). On adaptive estimation in stationary ARMA processes. Ann. Statist. 15, 112-133. Le Cam, L. (1986). Asymptotic Methods in Statistical Decision Theory. Springer-Verlag, New York. Le Cam, L. and Yang, G. L. (1990). Asymptotics in Statistics. Springer Series in Statistics, Springer, Berlin.
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Maercker, G. (1997). Statistical Inference in Conditional Heteroskedastic Autoregressive Models. Shaker, Aachen. Mύller, U. U. and Wefelmeyer, W. (2000a). Estimating parameters of the residual distribution in nonlinear regression. In preparation. Mύller, U. U. and Wefelmeyer, W. (2000b). Regression type models and optimal estimators. In preparation. Ogata, Y. (1980). Maximum likelihood estimates of incorrect Markov models for time series and the derivation of AIC. J. Appl. Probab. 17, 59-72. Pollard, D. (1985). New ways to prove central limit theorems. Econometric Theory 1, 295-314. Schick, A. (1993). On efficient estimation in regression models. Ann. Statist. 21, 1486-1521. Correction: 23 (1995), 1862-1863. Schick, A. (1999). Efficient estimation in a semiparametric heteroscedastic autoregressive model. Technical Report, Department of Mathematical Sciences, Binghamton University, h t t p : //math. binghamton. edu/ant on/preprint. html Schick, A. (2000). On asymptotic differentiability of averages. Probab. Lett. 51, 15-23.
Statist.
Schick, A. (2001). Sample splitting with Markov chains. Bernoulli, 7, 33-61. Schick, A. and Wefelmeyer, W. (1999). Efficient estimation of invariant distributions of some semiparametric Markov chain models. Math. Meth. Statist. 8, 426-440. Schick, A. and Wefelmeyer, W. (2000). Estimating the innovation distribution in nonlinear autoregressive models. To appear in: Ann. Inst. Statist. Math. Schick, A. and Wefelmeyer, W. (2001). Estimating invariant laws of linear processes by [/-statistics. Technical Report, Department of Mathematics, University of Siegen. http://www.math.uni-siegen.de/statistik/wefelmeyer.html Wefelmeyer, W. (1991). A generalization of asymptotically linear estimators. Statist. Probab. Lett. 11, 195-199. Wefelmeyer, W. (1994). Improving maximum quasi-likelihood estimators. In: Asymptotic Statistics (P. Mandl, M. Huskova, eds.), 467-474, Physika-Verlag, Heidelberg. Wefelmeyer, W. (1996).
Quasi-likelihood models and optimal inference.
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24, 405-422.
Wefelmeyer, W. (1997a). Adaptive estimators for parameters of the autoregression function of a Markov chain. J. Statist. Plann. Inference 58, 389-398. Wefelmeyer, W. (1997b). Quasi-likelihood regression models for Markov chains. In: Selected Proceedings of the Symposium on Estimating Functions (I. V. Basawa, V. P. Godambe and R. L. Taylor, eds.), 149-173, IMS Lecture Notes-Monograph Series, Institute of Mathematical Statistics, Hayward, California. Wefelmeyer, W. (1999). Efficient estimation in Markov chain models: an introduction. In: Asymptotics, Nonparametrics, and Time Series (S. Ghosh, ed.), 427-459, Statistics: Textbooks and Monographs 158, Dekker, New York.
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Institute of Mathematical Statistics LECTURE NOTES — MONOGRAPH SERIES
NUISANCE PARAMETER ELIMINATION AND OPTIMAL ESTIMATING FUNCTIONS T. M. Durairajan and Martin L. William Loyola College, Madras, India
Abstract In the context of obtaining optimal estimating functions for interesting parameters in the presence of nuisance parameters in parametric models, a method of elimination of nuisance parameters is proposed in this paper. The proposed method is direct and does not impose any 'factorization' conditions on the likelihood. In this direction, a sequence of lower bounds for the variance-covariance matrix of estimating functions is derived. A recipe which gives a transparent approach for obtaining optimal estimating functions is suggested. It is shown that minimum variance unbiased estimators could be obtained using the recipe. Keywords and Phrases: Lower bounds, nuisance parameter elimination, optimal estimating function.
1
Introduction
In the theory of estimating functions applied to parametric models involving nuisance parameters, the 'elimination' of nuisance parameters to obtain optimal estimating functions (EF) for interesting parameters is a very important task. In a pioneering work, Godambe (1976) suggested a method of eliminating nuisance parameters by multiplying and adding suitable functions to the score function and formally established the optimality of conditional score function. Lloyd (1987) and Bhapkar and Srinivasan (1993) claimed the optimality of marginal score function. However, that there are errors in the results of Lloyd (1987) and Bhapkar and Srinivasan (1993) has been pointed out by Bhapkar (1995, 1997) who imposed some more conditions and established the optimality of marginal score function. The conditional and marginal factorization properties were used by the above authors in the elimination of nuisance parameters. Heyde (1997) proposed a method of
238
DURAIRAJAN
AND WILLIAM
obtaining optimal EF by eliminating nuisance parameters from a suitably chosen function that possesses the 'likelihood score property'. Heyde gives the optimal EF of 'first order theory' but not of the higher orders. The present work is an attempt in this direction. In this paper, a straight forward recursive method of elimination of nuisance parameters without going into the factorization aspects of the likelihood is proposed. In this direction, a theorem which gives a sequence of lower bounds for the variance-covariance matrix of the EFs is established in Section 2. This is achieved by considering higher order derivatives with respect to the nuisance parameters drawing inspiration from Godambe (1984). Consequently, a recipe which gives a systematic approach for possible elimination of nuisance parameters leading to optimal EF is suggested. Section 3 presents several examples to illustrate the recipe. In Section 4, as another outcome of the main result of Section 2, a sequence of lower bounds for the variance - covariance matrix of unbiased estimators of the interesting parameters is given. This sequence is different from the sequence of Bhattacharya bounds both in context and in content. Further, it is shown that minimum variance bound unbiased estimators of the interesting parameters could be obtained by the suggested recipe.
2
The Main Result and the Recipe
Let X be a random vector with sample space X and probability density function p(x; ω) with respect to some σ-finite measure μ on (X, B(X)). The family of densities is indexed by ω = {θ,φ) E Ω with θ G Ωi C SRr, φ E Ω2 C 3?m, Ω = Ωi x Ω2. The interesting parameter is θ and the nuisance parameter is φ and estimation of θ in the presence of φ is considered. We assume the usual regularity conditions on the density function 'p' and the EFs g = (gu .. .,gr)': X x Ωx -» W (refer Godambe (1976, 1984), Bhapkar (1995, 1997)). Let Dg = ((E(dgi/dθj))). Let the class of EFs satisfying the regularity conditions be denoted as Go let Mg(ω) = D~ιE{g.g')(D'g)~ι, the variance-covariance matrix of standardized EFs. In the sequel, the following notations are used: le = (dlog p/dθu...,dlogp/dθry In = E(lθ l'θ)
(2.1) (2.2)
NUISANCE PARAMETER ELIMINATION
239
with l
φ \ — h\ )
&
l
•'22 — -^ [*0 " φ J
^ J
/ i i a n d / ^ a r e a s s u m e d non-singular a n d for simplicity, we write I,1' = lφ,
/&> = /i2, I$? = hi, J& = hi- Let (2.6)
, fc = 1 , 2 , . . .
Since / ^ are positive definite we have Bk+i > Bk. Also, E[L •0(*)
'j = BΓ1
V k.
(2.7)
Theorem 2.1: For every 3 € C/o, M5 > 5 fc , k = 1,2,..., with equality if and only if g = *)* = >1(0,0) L ^ where A(θ, φ) is a non-singluar matrix and the functions Lg ' are defined recursively in (2.4) and (2.5). Proof: For g e Go, we observe that E[glφk)>) = 0, E[gLf]'} Now, considering the n.n.d. matrix E
r(*)
9,' — =
-Dg
= -Dg\/k.
(2.8)
E(g.g')
and applying matrix theory arguments, we get Rank
- Rank
0 E{g.g')
Also, Bkι — M~ι > 0 by the non-negative definiteness of the full matrix in (2.8). This gives Mg > Bk. Further, B~ι - M~ι = 0 if and only if the rank of the matrix in (2.8) is r. ' for some non-singular matrix A(θ,φ), then Now, if g = A(θ,φ) clearly the matrix in (2.8) has rank r so that Mg = B^. Conversely, if Mg = Bk i.e. the rank of the matrix in (2.8) is r, then as B^1, Dg and E(g.g') are all non-singular, it is necessary that for some non-singular matrix A(θ, φ), g = A(θ, φ) - Lf\ Hence the theorem. Remark 1: If for some k > 1, Bk is attained by the EF A(θ,φ)Lf) for a suitable choice of A(θ,φ) (i.e. A(θ,φ)Ly is free of φ), then we have /Jί;+1) = 0 which gives L^+l) = L{θk) and Bk+λ = Bk. Similarly, V s > k + 1, /W = 0, L{θs) = Lf] and Bs = Bk.
240
DURAIRAJAN AND WILLIAM In view of this, we now propose the following.
Definition 2.1: If there exists a g* G Go such that Mg* attains a lower bound Bk for some A;, then g* is said to be minimum variance bound estimating function (MVBEF). Based on the theorem established and the above remark, we suggest the following recipe for eliminating nuisance parameters and obtaining MVBEF: "Starting with the score function /#, consider recursively the functions Lθ
= IQ — I ^ I ^ l φ ' i LQ = L Q — l[2 I22
lφ
a n
ds 0 forth. If t h e nuisance
parameters are essentially eliminated or appear as a multiplicative factor of an EF in some recursion, stop the process as the EF thus obtained is optimal and further recursions would result in the same EF". Remark 2: The first order bound in the sequence of bounds derived above namely Bι = (In — Iul^hi)"1 was derived as the lower bound by Chandrasekar and Kale (1984) who gave a different line of proof. In a latest book, Heyde (1997) has proposed a 'first order' theory for obtaining optimal EF. He suggests the possibility for higher order theory but does not give any explicit method for the same. The recipe suggested above gives a formal and transparent method to proceed to second and higher order theories and carries out Heyde's suggestion. However, the forms of the optimal EFs obtained in Theorem 2.1 do not follow as a consequence of the technique of Heyde (1997).
3
Applications
In this section, a number of examples are discussed to illustrate the recipe suggested in the previous section. Throughout this section, we reserve the symbol θ for the interesting (real or vector) parameter. Example 3.1: Let x = (xi,...,x n ) and y = (j/i,. ,J/n) be independent where X{ are i.i.d. with density φexp(-φx), x > 0 and yι are i.i.d. with density φθ~ιexp(-φθ~λy), y > 0, 0, > > 0 . Here,
is the MVBEF attaining the bound B\. Example 3.2: Let z\,..., zn be i.i.d. with z% = (x^, yu > ? VH) where X{ are i.i.d. exponential with mean φ and for each fixed j — 1,..., r, y^ are i.i.d. n
exponential with mean φθj. Denote x = Σ x^ yj = Y%=i yji, j = 1,..., r.
241
NUISANCE PARAMETER ELIMINATION
Here, φL™ = (rf,... ,g*r) is MVBEF, with g* = | - ^
^
Σ |
Remark 3: Examples 3.1 and 3.2 have been discussed respectively by Lloyd (1987) and Bhapkar and Srinivasan (1993) in the context of marginal factorization of the likelihood. These authors claimed that a marginal score function is the optimal EF. However, from the above discussion, we find that the optimal EFs obtained above do not coincide with the EFs claimed by these authors as optimal. In Example 3.1, we have Mg{\)+ — 2θ2/n whereas for the EF of Lloyd (1987) namely g0 = n/θ - 2n/(θ + we have Mgo = 2(n + I)θ2/n2 > M (i)*. This shows that Lloyd's claim that go is optimal EF is incorrect. The errors in Lloyd (1987) and Bhapkar and Srinivasan (1993) has been pointed out also by Bhapkar (1995, 1997) who has found the correct optimal EF for the model in Example 3.1 but not for Example 3.2. In contrast, the recipe of Section 2 and the explicit form L,θ ' for the optimal EF have enabled us to achieve this for Example 3.2 as well in an elegant manner. Example 3.3: Let x\, yi,..., x n , yn be independent normal with E(xi) = 0, E(yi)
=θ + φi, V{xi) = V(yi) = 1. Here, L^ = Σ {x{ - θ) is the MVBEF. i l
Example 3.4: Let a i, j/i,... .Xn^Vn be independent normal with E(x{) = θ + φu E{yi) = φi, V{xi) = V{yi) = 1. Here, the MVBEF is L^ = n(x - y - θ)/2. Remark 4: Examples 3.3 and 3.4 were discussed by Godambe (1976) in the context of nuisance parameter elimination when conditional factorization property for the likelihood holds good. He has shown that the same EFs are optimal. In the above discussion, we have demonstrated the straight forward applicability of our recipe without investigating the factorization aspects which is required in Godambe's approach. Example 3.5: Let x = (xi,... ,xn) and y = (yi,... ,y m ) be independent where xι are i.i.d. Poisson (0>), yj are i.i.d. Poisson (>), θ,φ > 0. Here,
4
υ
= mn(x - θy)/(θ(nθ + m)) is the MVBEF.
This example with m — n — \ has been discussed by Reid (1995) in illustrating the roles of conditioning in inference in the presence of nuisance parameters, wherein the estimation is based on conditioning upon a statistic called a 'cut' (Barndorίf-Nielsen 1978) and involves a suitable reparametrization. In contrast, our approach is straight forward and does not require reparametrization. Example 3.6: Consider the linear model of a randomized block design Vij = μ + U + bj + eij, i — 1,..., fc, j = 1,..., r where e^ are i.i.d. iV(0, σ 2 ),
242
DURAIRAJAN AND WILLIAM
Σt{ = Σbj
= 0. Suppose estimation of t h e effect of the first treatment 't'λ
alone is of interest. 2
T h a t is θ = t\, φ = ( μ , ΐ i , . . . ,ίjfe_i,&i, {
Here, (σ (k
2
5
&r-i )
= ylm - y.. - h is MVBEF, where ylm =
- l)/(kr))L ^
Example 3.7: Consider a 2 x 2 contingency table ((n^)), i, j = 1,2, following a multinomial distribution with fixed sample size n = ΣΣn^ and with probabilities ((TΓJJ)), i,j — 1,2, ΣΣπ^ = 1. Let θ = πn be the parameter of interest with φ = (πi2,π2i). Here Lβ ' = {n\\ — nθ)/(θ(l — θ)) is the MVBEF. This example was discussed by Bhapkar (1989) in investigating conditioning and loss of information in the presence of nuisance parameters. Example 3.8: Let {X(t),t > 0} and {Y(t),t > 0} be two independent Poisson processes with parameters (θ + φ) and φ respectively, 0, φ > 0. Suppose data on the states of {X(t)} at times
( Let
1
lt is f o u n d
t h a t
-1
1
2^
2
get 5 ( )* = A(θ, φ) 4
^2
n-lV
2_
^ = ώ . Σ K - %) 2 Choosing Z— 1
1 ,n
2 )
= (Sf - σf,...
Φ) =
—
) '
j
V(: as the
|4'
Ί4) We
MVBEF attaining
the bound B2. This MVBEF was shown as optimal EF not attaining the bound j?i by Chandrasekar and Kale (1984) and in their framework served as an example of an optimal EF which is not MVBEF. From our discussion above, it is found that g^* is MVBEF attaining, however, the higher bound B2 Example 3.10: Let xi, yi,..., x n , yn, be independent normal with E(xι) = E(yi) = φi, i = 1,..., n and Vfa) = V(yi) =θ Vi = 1,..., n. Here, L^ is
NUISANCE
PARAMETER
ELIMINATION
243
not an E F for 0 and so we proceed to the second recursion to get (2) θ
n 1 A Q 9Λ ~*~ AΛ2 ^ Λ X * ~" y*) 2=1
a s
MVBEF attaining the bound B2.
The above example has been discussed by Godambe (1976) in the context of conditional factorization wherein he contrasts the consistency of the solution of the above optimum estimating equation with the inconsistency of the usual maximum likelihood estimate discussed by Neyman and Scott (1948). Again, investigation into factorization aspects is not required in our approach. Example 3.11: Let #1, yi,..., xni yn be independent normal with E(xi) = 0, E{yi) = φ, V(xi) = V{yι) = 0, φ e 5R, 0 > 0. Here, L J 1 } is not an EF. So, we proceed to the second recursion to get Lg ' = —^[nθ2 4- (2n — 1)0 — n s ( l + sl + x2)] a s the MVBEF attaining bound B2. Here, si = ^(xi - x)2 and 5^ = ^Σ(yj — y) 2 . The solution of the equation LQ = 0 is a consistent estimate namely Λ
^ 4
[(2n - I) 2 + 4n 2 [s2x + ^ + x 2 ) ] V 2 - (2n ^
Minimum Variance Unbiased Estimators
The main result of Section 2 leads us to minimum variance bounds for unbiased estimators of the interesting parameters. Prom Theorem 2.1, it is immediately evident that, for unbiased estimators T = (Ti,...,T r ) ; of Var - Coυ{T) > Bk, fc = 1,2,...
where Bk's are given in (2.6). This is verified by considering EFs of the form T-0. If any of the L ^ ' s defined recursively in (2.4) and (2.5) is such that A{θ,φ)L{θk) is of the form T* - θ for a suitable choice of A(θ,φ), then T* is minimum variance unbiased estimator (MVUE) of θ. Thus, the recipe of Section 2 could possibly be of help in finding T*. The following examples illuminate this point. Example 4.1: Consider the model in Example 3.3. Here LQ ' /n — x — θ so that x is MVUE of θ attaining bound B\. Example 4.2: Consider the model in Example 3.4. Here 2L,Θ '/n = x — y — θ so that x — y is MVUE of θ attaining bound B\.
244 Example 4.3: 2
(σ (fc - l)/kr)L^
DURAIRAJAN AND WILLIAM Consider the linear model in Example 3.6.
Here,
= ylm - y.. - tλ so t h a t ylm - ymm is M V U E of tλ.
Example 4.4: Consider Example 3.7. Hear, 0(1 - θ)Ly /n = n\\jn - θ so that nn/n is MVUE of θ. Example 4.5: Consider Example 3.8. Here, ((0 + φ)sntm)~1Lg [SnX(tm) - tmy(Sn)]/(Sntm) as MVUE of θ. Example 4.6: Consider Example 3.9. (σ\,..., σ2) attaining bound i?2
= 0 gives
Here, (S?,... ,Sj?) is MVUE of
Example 4.7: Consider the Neyman-Scott model in Example 3.10. Here 2θ2L%)/n = Σ{xi - yi)2/(2n) - θ so that Σ{Xi - y;)2/(2n) is MVUE of θ attaining bound B<ι. It is noted that the MVBEF need not produce MVUE when it cannot be reduced to the form T* — θ. This is evident in Examples 3.1, 3.2, 3.5 and 3.11. This fact is also reported by Thavaneswaran and Abraham (1988) who considered EFs for non-linear time-series models. Acknowledgement We thank the referee for bringing to our notice some of the important references in this area and for the valuable comments which improved the quality and content of the paper substantially.
References Barndorίf-Nielsen, O.E. (1978) Information and Exponential Families in Statistical Theory. Wiley, New York. Bhapkar, V.P. (1989). Conditioning on ancillary statistics and loss of information in the presence of nuisance parameters. J. Statist. Plann. Inference, 21, 139-160. Bhapkar, V.P. (1990). Conditioning, marginalization and Fisher information functions. Proc. R.C. Bose Symposium, Delhi. (Ed. R.R. Bahadur). Wiley Eastern Limited, New Delhi, 123-136. Bhapkar, V.P. (1991). Loss of information in the presence of nuisance parameters and partial sufficiency. J. Statist. Plann. Inference, 28, 185-203. Bhapkar, V.P. (1995). Completeness and optimality of marginal likelihood estimating equations. Comm. Statist. A - Theory Methods, 24, 945-952.
NUISANCE PARAMETER ELIMINATION
245
Bhapkar, V.P. (1997). Estimating functions, partial sufficiency and insufficiency in the presence of nuisance parameters. Proc. Symposium on Estimating Functions, Georgia. (Ed. I.V. Basawa, V.P. Godambe and R.L. Taylor). Institute of Mathematical Statistics: Lecture Notes Monograph Series. 32, 83-104. Bhapkar, V.P. and Srinivasan, C. (1993). Estimating functions : Fisher Information and optimality. Probability and Statistics. Proc. First International Triennial Calcutta Symposium on Probability and Statistics. (Ed. S.K. Basu and B.K. Sinha). Narosa Publishing House, New Delhi, 165-172. Bhapkar, V.P. and Srinivasan, C. (1994). On Fisher information inequalities in the presence of nuisance parameters. Ann. Inst. Statist. Math. 46, 593-604. Chandrasekar, B. and Kale, B.K. (1984). Unbiased statistical estimation functions for parameters in presence of nuisance parameters. J. Statist. Plann. Inference, 9, 45-54. Godambe, V.P. (1976). Conditional likelihood and unconditional optimum estimating equations. Biometrika, 63, 277-284. Godambe, V.P. (1984). On ancillarity and Fisher information in the presence of a nuisance parameter. Biometrika, 71, 626-629. Heyde, C.C. (1997). Quasi-Likelihood and its application - A general approach to optimal parameter estimation. Springer, New York. Lloyd, C.J. (1987). Optimality of marginal likelihood estimating equations. Comm. Statist. A - Theory Methods, 16, 1733-1741. Neyman, J. and Scott, E.L. (1948). Consistent estimates based on partially consistent observations. Econometrica, 16, 1-32. Reid, N. (1995). The roles of conditioning in inference. Statistical Science, 10, 138 - 157. Thavaneswaran, A. and Abraham, B. (1988). Estimation for nonlinear time - series using estimating equations. J. Time Ser. Anal. 9, 99
247 Institute of Mathematical Statistics
LECTURE NOTES — MONOGRAPH SERIES
OPTIMAL ESTIMATING EQUATIONS FOR MIXED EFFECTS MODELS WITH DEPENDENT OBSERVATIONS Jeong-gun Park and I.V. Basawa University of Georgia Abstract Optimal joint estimating equations for fixed and random parameters are derived via an extension of the Godambe criterion. Applications to autoregressive processes and generalized linear mixed models for Markov processes are discussed. Marginal optimal estimating functions for fixed parameters are also discussed. Key Words: Optimal Estimating Functions; Generalized Linear Mixed Models; Autoregressive Processes; Markov Processes.
1
Introduction
Mixed effects models containing both fixed and random parameters are used extensively in both applied and methodological literature. A review of linear mixed models and their applications is given by Robinson(1991). Generalized linear mixed models are discussed by Breslow and Clayton(1993) among others. Work on the extension of mixed effects models to dependent observations appears relatively scarce. Our main goal in this paper is to develop optimal estimating equations for mixed effects models with dependent observations. See Basawa et al.(1997), Heyde(1997), and Godambe(1991) for recent literature on optimal estimating functions. Desmond(1997) gives an overview of estimating functions. Suppose Yt is a vector of observations on n individuals at time £, and Y(t — 1) = (YΊ,..., Yt-ι). Conditional on Y(t — 1) and a random parameter 7, the density of Yt is denoted by p(yt\y{t — l),/3,7) where β is a fixed parameter. Let π(7|α) denote the (prior) density of 7 which may depend on a parameter a. Suppose, for simplicity, a is known, and we wish to estimate β and 7 from a sample Y{T) = (Yi,..., Yτ). The likelihood function, conditional on 7, is given by ) =P(yo)TiJ=lP(yt\y(t-
l),β,j).
(1.1)
248
PARK AND BASAWA
The joint density of 7 and Y(T) is p(7,v(T)|α,/?)=LGS,7)π(7|α).
(1-2)
An intuitive way, often used in practice, to estimate the "mixed effects" β and 7, is to maximize p(7,y(T)|α,/3) with respect to β and 7 and obtain formally the estimating equations : of
dlogL(β,j) 97
°y=0, +
(i.3)
d/ogπ(7|α) ^7
= Q
Example 1. Linear mixed models Take T = 1, and YQ = yo fixed(given). Suppose, conditional on 7, Y\ is normal with mean vector X β + Z 7 and covariance matrix Σ, where X and Z are known covariate matrices. Further, assume that 7 is a normal vector with mean zero and covariance matrix Γ. It is assumed, for simplicity, that Σ and Γ are known. Equations (1.3) and (1.4) then lead to the well known mixed linear model equations, see, for instance, Robinson(1991) for a review. Example 2. Generalized Linear Mixed Models Again, set T = 1, and suppose (1-5)
), and Var\Yλ\β,η] = V(β,Ί) = U(μ(β,Ί)).
(1.6)
Without further assumptions regarding the conditional density of Y\ given 7, one may be interested in estimating β and 7. If we choose (1.7)
h(μ(β,Ί))=X'β + Z'Ί,
for an appropriate link function /ι( ), and retain the normality assumption regarding 7 (i.e. 7 ~ iVίo, Γj), a penalized quasi-likelihood approach (see Breslow and Clayton( 1993)) yields the estimating equations : (1.8)
)-1(Y1-μ)-Γ-1Ί
where μ = μ(β,j)
= 0,
(1.9)
= hΓι{X'β + Z'j) = g(X'β + Z'j), say. Equations
(1.8) and (1.9) correspond to (1.3) and (1.4) if the conditional density of
249
OPTIMAL ESTIMATING EQUATIONS
Y\ given 7 is a member of an exponential family. See also Sutradhar and Godambe(1997), and Waclawiw and Liang(1993). Analogous to (1.8) and (1.9), we now propose a general method based on the penalized quasi-likelihood equations for dependent data. Let (1.10)
E[Yt\Y(t-l),βΠ]=μt(β,Ί): and Var[Yt\Y(t-l),β,Ί] = Vt(β,Ί).
(1.11)
Suppose further that the prior density of 7 is known to be π(7|α). Consider the estimating equations: (1.12)
( L 1 3 )
If the conditional density of Yt given Y (t — 1) and 7 belongs to an exponential family, the equations in (1.12) and (1.13) correpond to (1.3) and (1.4). Suppose that 7 has a prior density τr(y\a) with mean 0 and variance Γ(α). Consider a modified equation for 7 : E
[iaJ^^\
Γ(α)"'7 = 0. (1.14)
If 7 - N(θ, Γ(α)), we have
_
dlog-κ(η\ά) dη
Hence, in this special case, (1.14) reduces to (1.13). We show in this paper that the equations in (1.12) and (1.14) are optimal estimating equations in the sense of a generalized Godambe criterion. The question of the performance (sampling properties) of the estimates obtained from (1.12) and (1.14) needs to be addressed via asymptotics. In the special case of linear mixed models (example 1), the estimates are known to be best linear unbiased predictors(BLUP), see Robinson(1991). In the general case, we may use an extension of the asymptotic optimality criterion discussed by Wefelmeyer(1996), at least for the estimation of the fixed effects parameter β. See also Heyde(1997). This topic will not be considered in this paper.
250
PARK AND BASAWA
In general, the information matrix(or its estimate) corresponding to the optimal estimating functions can be used to compute the standard errors of the estimates. The paper is organized as follows. The general optimality criterion for the estimation of mixed effects is introduced in Section 2. The optimal estimating equations are derived in Section 3. Section 4 discusses applications to autoregressive processes and generalized linear mixed models for Markov processes. Section 5 considers an alternative method based on a marginal model specification. Finally, Section 6 contains some concluding remarks on work in progress.
2
Optimality Criterion
Let y be the sample space, (Θi x Θ2) C Rk the parameter space, where Θi C Rm,m < k. Assume that 71^(7) is a prior density of 7 for a fixed /?, where 7 € Θi and β e Θ2. Let C be the set of all functions g : y x (Θi x Θ 2 ) -> Rk such that E\g(Y,j,β)\β] = 0, V/3 E Θ 2 , where the expectation is with respect to the joint distribution of Y and 7, for a fixed β. Assume that E[g{Y,η,β)g(Y,η,β)'] is finite for any g £ £. We shall use the notation < gug2
>β= E[gι{Y,Ί,β)g2{Y,Ί,β)'\β], V J l j f t 6 A
(2.1)
where the expectation is with respect to the joint distribution of Y and 7, for a fixed β. Let p(Y, 7, β) denote the joint density of Y and 7. We assume throughout that the following conditions are satisfied : C.I. For any g € £, g is differentiate with respect to both 7 and β\ Both E[%] and E[%) exist. C.2. The joint density p(y, 7, β) is differentiate with respect to both 7 and β. The support of p(y,7,/3) does not depend on the parameters. C.3. For any g G £, E[g] is differentiate with respect to β under the integral sign. CΛ. The support of conditional density Pβ(y\j) does not depend on the parameters 7 and β. For any g G £, i?[#|7] is differentiate with respect to 7 under the integral sign; E[^E{g\Ί)] and E[E(g\j)dl°9^h)] exist. The above conditions ensure the existence of various quantities in (2.4) and the validity of the derivation of the information function defined in (2.6) below.
OPTIMAL ESTIMATING EQUATIONS
251
Let s = ( s i , 5 2 , . . •, Sfc), where
,
dlogp(Y,y,β)
s
,
dlogp{Y,η,
sm+ι=
j =
dβi
For any g € £ 0 , A) C £,
^M = E
dlogp(Y,Ί,β)' 1
, j = l,...,m.
Note that p(Y,j, β) = Pβ{Y\Ί)κβ{Ί)i where pβ{Y\^) is the conditional density of Y given 7 with respect to an appropriate measure μ(y) and πβ(j) is the density of 7 with respect to a measure 1^(7). We then have E[gSj]
= E
dlogpβ(Y\-y)
dlogπβ(j)
dΊj
dΊj
f
= E = E
dE\g\Ί]\
dg
\dlogπβ(j)
E[g\l] • (2.2)
Now,
E[gsm+ι]
= E^g
dlogp(Y,Ί,β)
f dp{y, Ί, -dμ(y)dυ(j), I = 1,..., k - m.
J
Oui
(2 3
>
Combining (2.2) and (2.3), we obtain dg
/ J
^ Γ ^ 1Λ (2.4)
Note that if E\g\η] = 0, (2.4) reduces to
(2.5) LC/p J /
We define the information function by Ig(β) = E[gs]Έ[gg]~ιE[gs],
(2.6)
for any g E £o5 where E[gs] is given by (2.4). The criterion of optimality is to maximize the information function Ig{β) over J G £ Q
252
PARK AND BASAWA
Definition 2.1 A function g* is an optimal estimating function in Co if I9.(β)-Ig(β) is nonnegative definite, for all g E Co and all β. Case I (Fixed Effects) : m = 0, i.e. the model involves only the parameters of fixed effects. When m = 0, E[gs'} — -£?[||]. So the information function is given by
Let g* be the optimal estimating function for β in £o Then
It is easily verified that the nonnegative definiteness of Ig*{β) — Ig{β) is equivalent to that of E(gg) -
H{H*)-'E[g*g*']{H*')-lH'.
The latter turns out to be the optimality criterion given by Godambe(1985) when only fixed parameters are present with H = E \-ga\ and H* = E -A- . See also Godambe(1960) and Durbin(1960). Case II (Random Effects) : ra = fc, i.e. the model involves only the parameters of random effects.
When m = k, E\gs) = -E [f}] + E [ ^ 1 + ^ | 7 ] « 2 ^ 2 i ] . Thus the information function is given by Ig(β) = j'E[gg'}J,
where J = -E [^] + E [ ^ M
+
E[g\Ί]dl°9^{Ί)] . Let g* be the optimal
estimating function for 7 in Co- Then we require Ig*{β) - I9(β) = J*'E[g*g*'}J* - JE[gg]J to be nonnegative definite. This turns out to be Chan and Ghosh(1998)'s optimality criterion when only the parameters of random effects are present and J* is J with g replaced by g*. See also Ferreira(1981, 1982) and Godambe(1998).
253
OPTIMAL ESTIMATING EQUATIONS
3
Optimal Estimating Equations
Here we derive optimal estimating functions for parameters of mixed effects. Let y be the sample space and F? the σ-field generated by a specified partition of y. Let hi be a real-valued function of Y, 7, and β such that = 0, < = l , 2 , . . . , n .
Let u( ,β) :Θι^Rm
with E[u( ,β)] = 0, forfixedβ.
We consider the linear estimating space given by
B(β)u(Ί,β)\ , where 0^(7,/3) is a k x 1 vector which is measurable with respect to the σ-field Flf and B(β) is a, k x m non-random matrix. Let
α*(7,/?) = -E[(^ί, ?jjf) l*f ,7,/{ ^αr(/^ > 7 ,/3)]^
(3.1)
and
(3.2)
Theorem 3.1 Let 9* = Suppose that hi's are mutually orthogonal in the sense that E[h*h*j \F^, 7, /3] = 0 for alii φ j , ij = 1,2, . . . , n ; wΛere ΛJ =a*(η,β)hi. Then g* is an optimal estimating function in £Q Proof: From C h a n a n d Ghosh(1998), it is enough t o show t h a t g* is a n orthogonal projection of s into £o> i-e., < g,s — g* >= 0 for any # G CQ. We have
=
}
E[ajhjS ] + BE[us }
\Fί,Ί,β]\ +BE[us'].
254
PARK AND BASAWA
From (2.4), since E[hi\FY^,β]
= 0 for all i and any β,
Also, from (2.4), we have
-L - \u Since the function u is only a function of 7 and 5, the conditional expectation of ti, conditional on 7 and 5, is u itself. Thus we have
Next the second term on the righthand side of (3.3)can be found as
2=1.7=1
[[aM^\F^Ί,β)] +BE[uu]B*'. Since the functions aihi and a^hj are orthogonal for all i
*=1 j=l
Substituting α^ and J5*, we get
(3 5 )
Hence, from 3.4 and 3.5, we have < g,s > — < g,g* >= 0. This complete the proof.
Independent Observations If the elementary estimating functions h{, i = 1,..., n are independent with £7[/ii(y, 7, /?)|7, /?] = 0, Vi = 1,2, . . . , n , it's not necessary to partition y i.e. Fj is y itself. For an example, if Y = (y\,y2, 52/n) and y^'s are
255
OPTIMAL ESTIMATING EQUATIONS
independent, we take hi to be a function of yι, 7 and β such that E[hi\^, β] = 0, Vi. Here h^s are independent. Hence, the optimal estimating function in the space Co is given by g* in Theorem 3.1 with α*(7,/3) replaced by
a?(Ί,β) = -E [ ( | ^ , 0 ) |7,/3J [Fαr^lT,/?)]-1.
(3.6)
Application to discrete time stochastic processes As an example of dependent data we develop an optimal estimating function for a discrete time stochastic process. Let {Yi, Y2,..., YT} be a discrete time stochastic process. Let ht be a real-valued function of YΊ,..., Yj, 7, and /? such that
where i* 1 ^ is the σ-field generated by the past observations Yi, Y2,..., Yt-ι Let u(Ίβ) : Θi -> i ϊ m with E[tz( ,/3)] = 0, for fixed β. We consider the estimating space
where αί_ 1(7, β) is a A; x 1 vector measurable with respect to F£_ι and is a k x m non-random matrix. Let
and B*(β)=E\[u(Ί,l (3.8)
Theorem 3.2 Let T α
* = Σ t - i ( 7 , / ^ t + B*{β)u{Ί,β). t=\
Then g* is an optimal estimating function in CoThe proof follows from Theorem 3.1 with Fj = F^_x.
PARK AND BASAWA
256
4
Applications
In this section, we will discuss two applications and demonstrate the derivation of optimal estimating functions.
4.1
Autoregressive Processes
Suppose that yt(j), t = 1,2,..., T, j — 1,2,..., n are observed at time t on the j t h subject from the first order autoregressive process(AR(l) process), (4.1) and (4.2)
φ(j) = x'jβ + zjΊ,
where 7 ~ JVu),Γj and εt = (εί(l), .. ,εt(n))',ί = 1,2,... ,T, are iid random vectors with E[εt] = 0 and Vαr[εί] = Vn(a). Assume that 7 and εt are independent for any t. Here β is a (ra x 1) vector of fixed parameters and 7 is a (g x 1) vector of random parameters, and Xj and Zj are vectors of known covariates. Note that we are not making distributional assumptions regarding εt other than the mean and variance assumptions. Let yt = (y t (l),...,y t (n))\
φ=
and
0 0 .
0
0
yt-i(n)
Then (4.1) can be written in a vector form
We consider optimal estimation for (7, β) assuming a known. We choose elementary estimating functions ht and u such that £J(/ιί|F^_1,7,/3) = 0 and
E(u\β) = 0. Let ht = yt-Yt-ι{X'β
+ ZΊ)
and u = 7,
where X = ( x i , . . . , x n ) and Z = (z\,... , z n ) . Consider the estimating space £0 = {ff : ff = Σ)^=i At-ιht we let
+ i?u}. Now
257
OPTIMAL ESTIMATING EQUATIONS and
where π(η) is the prior distribution of 7. Then A^_x and B* are computed as A*_i =
( χ)
t-Ma)-' YM)-'
and d B* B*=
11
ί "£*« \ Γ" Γ".
Thus, the optimal estimating function for (7, β) in the space Co is given by g* = T
-ιVn{a)-1 (yt - Yt-ι(X'β + Z'Ί)) - T~ιΊ,
g\ =
(4.3)
and
= ΣXYt-iVn{aΓι (yt - Yt-ι(X'β + Z'Ί)).
(4.4)
ti t=i
Prom (4.3) and (4.4), the optimal estimates {y*,β*) of (η,β) are given by
ί-itί.ία)-1^* _ γt_lX'β*) I
7* = and
-1
β* = t=l
t-1
ί-l
t-l
where Δ = Z (ΣΪ=I Yt-iVnicή^Yt-i) Z' + Γ" 1 . Prom (2.4), the information function corresponding to the optimal estimating function g* is obtained as ί ZHnZ' + Γ" 1
\
XHnZ'
ZHnX' \
XHnX' J '
where Hn = ΣΪ=i ^ - i F ^ α ) - 1 ^ - ! ] . As a special case, if the subjects are uncorrelated, i.e. Vn(a) = diag(aj,j = 1,..., n), then the optimal estimating equations from (4.3) and (4.4) turn out to be n T j=l t = l
PARK AND BASAWA
258 and
n T V^V^
-1
/ ' Δ^ί 3=1 t=l
3
=°
/ \
y ι
L VJ
'
Thus the optimal estimates n
J
(TJ*,/3J
) of (7,/?) are obtained as
T
Ίi* = Δ j=l
t=l
and n
T
n
T
3=1
t=l
3=1
t=l
' n
T
1
n
Γ
(Σ Σ j=i t=i
LJ=I t=i
where Δ = Σ?=i Σ£=i ^fvliU)^
+ Γ"1.
We extend the method of obtaining optimal estimating functions to the p order autoregressive processes. Suppose that yt{j),t — 1,2, . . . , Γ , j = 1,2, . . . , n , are observed at time t on the j < / ι subject from the pth order autoregressive process(AR(p) process), th
(4.5)
Vtϋ) = ^2Φk(J)yt-k(J)+εt(j), k=l
and ΦU) = foiίi), • 1 ^ 0 ' ) ) = -Xj/Ϊ + ZjΊi
(4-6)
where 7 ~ Nq ίo, Γj and εt = (εt(l),..., ε*(n))', t = 1,..., T, are ΐid random vectors with E[εt] = 0 and Vαr[εt] = Vn(a). Assume that 7 and £* are independent for any t. Here β is a (m x 1) vector of fixed parameters, 7 is a (q x 1) vector of random parameters, and Xj and Zj are matrices of known covariates. Let
άι)
°
0
ypt(2)
0
0
••• ° ^
...
0
γ
tp=
V
••• ypt(n),
)
and ^ ( j ) = {yt-ι{j),yt-2U)i - ">yt-p{j))'- Elementary estimating functions ht and u for 7 and /? are chosen to be
259
OPTIMAL ESTIMATING EQUATIONS and
where X = (X(l),... ,X(n)) and Z = (Z(l),... ,Z(n)). These elementary estimating functions satisfy the required condition of unbiasedness, i.e, ElhtlF^^β] = 0 and #M/?] = 0. In the estimating space Co — {g : g = Σ*Li M-\ht + Bu}, the optimal estimating function for (7, β) is given by g** = (ffί*,^*) where T
Σ
gl* = £ ZY;tVn(a)-1 (yt - Ypt(X'β + Z'Ί)) - Γ ' S , t=ι
and gl* = ΣXY'vtVn{ά)-1 fa - Ypt(X'β + Z;7)) From gl* and 32*5 the optimal estimates of 7 and /? are found as Y* = A~ιZ {γ;tVn(a)-ι(yt
- YptX'β**)}
and Γ
+Vn(θl)'~lYnt \ X
n
t=l T
(
t=i
{
where Δ = Z(ΣLI 4.2
—ZA~~l. t=l T
K
t=i
J
YptV'1 (a)Ypt)Z' + Γ " 1 .
Generalized Linear Mixed Models for Markov Processes
Suppose that {yt(j),t = 0,1,..., Γ, j = 1,2,..., n} is a markov process with a transition density f(Vt(j)\Vt-ιU)>Φ(J)) = c exp{φ{j)mt{yt{j),yt-i{j))
~ qt(yt-i{J)>ΦU))} (4.7)
and xjβ + z'jΎ,
(4.8)
where 7 ~ JV(O,Γ) and c is a function of yt{j) and yt-ι(j). Here /3 is a (mxl) vector of fixed parameters, 7 is a (r x 1) vector of random parameters, and Xj and Zj are known vectors of covariates. It is assumed for simplicity that conditional on 7, the processes {yt{j)} are independent for different j = 1,2,...,n.
PARK AND BASAWA
260 Let X = (xι,x2,...,xn)
and Z = (zχ,Z2,. • • ,zn). Then (4.8) can be
written as
/ φ{\) \ φ(2)
Φ=
= X β + Zj.
We consider joint optimal estimation for (7, β), assuming that Γ is known. We choose elementary estimating functions ht and u for 7 and β such that Let
= rπt — qt and u = 7, where \
m t (y t (2),y ί _ 1 (2))
\
and qt =
™>t(yt(n),yt-i(n))
/ Consider the estimating space £o = {9 '• 9 = Σt=i -A-tht + Bu}. Let
A; = ~E[φ,§f Then we have
and
r-1, where ςft = diag {-Q^^qt{yt-ι(j),Φ{j))J = 1,... , n j . Thus, in the space £o the joint optimal estimating function for (7,/?) is given by g* = (^,^2)5 where n T
= ΣΣzj{ j z
and
m
t(ytU),yt-i(j))-qt(j))-r-1Ί,
(4.9)
n T
(4.10) The optimal estimates (7*,/?*) for (7,/3) can be obtained by solving the equation g* = 0 for 7 and /? simultaneously.
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OPTIMAL ESTIMATING EQUATIONS
Prom (2.4), the information function corresponding to the optimal estimating function 3* is obtained as
/ ZHnZ' + Γ- 1 ZHnX' \ XHnZ XHnX
\ I
Where Hn = ΣΪ=ι E[qt] We now illustrate the model by two examples. Example 1. Consider an AR(1) process with normal errors, i.e. yt(j) = Φ(j)yt-Λj) + εt(j)
(4.11)
φ[j) = χ.β + z'jΊ,
(4.12)
and
where εt(j) ~ indep iVίO,σ|J and 7 ~ iVίO,Γj. The conditional density is given by -ιϋ)iΦ(j)) =ceχp\-
^2(yt{j)-Φ{j)yt-Aj))
>,
(4.13)
where c = -Ί=^=—. Since (4.13) can be written as f(ytϋ)\yt-i(j),Φϋ))=c* we have mt{ytϋ),yt-ι{j)) = and
This gives μ t (j) = σ^y^ifiφij) and Viϋ) = σ^y^ij). Hence the optimal estimating function for (7,/?) is given by g* = (31,32)? where n T
and n 9*2 =
T
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PARK AND BASAWA
The optimal estimates of 7 and β are obtained by solving the equations gt = 0 and g\ = 0 which yields the same estimates as ήfj and β\ in section 4.1. Example 2. Let {yt{j)},t = 0,1,2,..., be a Markov chain, for each j = 1,2,..., n, defined on the binary state space {0,1}. Denote πtj = P(yt(j) = l|yt-i(j)), θtj = logit{πtj) = log ί γ ^ j — ) • We then have expjθtj} exp{θtj}' Consider the model θtj=βo + Φjyt-ι(j),
(4.14)
where φj = x'jβ + zfl- Conditionally on 7, the Markov chains {yt{j)}>J = 1,..., n, are assumed to be independent. Suppose 7 ~ Λf if), ΓJ. Conditional on 7, the transition densities are given by p(vtU)\Vt-i(j),Ί)
=
7rjJu)(l-^)(1-ytu))
=
exp{θtjyt(j)
=
exp{βoyt(j) + Φjyt-i(j)yt{j)
- logfl + ea?p{β
- log(l + exp{β0 + Φjyt The optimal estimating functions for (7,^,/?o) then reduce to n
Γ
n
Γ
and
The third estimating function g% here corresponds to the common intercept βo in the model for θtj
263
OPTIMAL ESTIMATING EQUATIONS
5
Marginal Quasi-likelihood Estimation
Let fit(y{t - l),β) = E\yt\yt-ι, • • ,yi,β], and Vt{y(t - l),β) = Var[yt\yt-ι,...,yi,β]. The optimal estimating equation for β is τ
Σ
/
0jH(v(t-l),β)\ Vt-\y(t-l),β)(yt--μt(y(t-l),β))=O.
(5.1)
Let β denote a solution of (5.1). Define μt{y(t - l),j,β) = E[yt\yt-u • ,2/i,7,/?L and t _i,...,yi 1 7,i9]. For fixed /3, let
denote an elementary estimating function for 7. Suppose 7 has a prior density π(7|α) with mean 0 and variance Γ. Consider the estimating equation T
Σ t=i
r - X 7 = 0.
(5.2)
For fixed j9, (5.2) is an optimal estimating equation when only the random parameter 7 is present in the model. We now substitute the marginal quasilikelihood estimate β in (5.2), when β is unknown. Denote the resulting estimate of 7(obtained from (5.2) after replacing β by β) by 7. The estimates β and 7 will be referred to as the marginal quasi-likelihood estimates(MQL). Note, however, that for fixed /3, (5.2) is the same as the estimating equation (1.14) for 7 corresponding to the joint optimal estimation of β and 7. It must be noted that (5.1) and (5.2) are not jointly optimal; on the other hand, (5.1) is optimal for β with respect to the marginal density of y = (y*,..., y\) and (5.2) is optimal for 7(when β is known) with respect to the joint density of y and 7. Application to Autoregressive Processes : Suppose that yt{j), t = 1,2,..., T, j = 1,2,..., n are observed at time t on the jth subject from the first order autoregressive process(AR(l) process): yt(j) = Φ(J)yt-i(j)+εt(j),
(5.3)
and = Xjβ + Zjj, where 7 ~ 7VρΓθ,r) and ε t = ( ε t ( l ) , . . . ,εt{n))\t
(5.4) = 1,2,...,T, are iϊd
random vectors with E[εΐ\ = 0 and Vαr[εt] = Vn(a). Assume that 7 and εt
264
PARK AND BASAWA
are independent for any t. Here β is a (m x 1) vector of fixed parameters, 7 is a (q x 1) vector of random parameters, and Xj and Zj are vectors of known covariates. Let (yt(l),---,»*(")) 1
Vt=
and ϊ t _ i = diag(yt-ι(j),j = 1,... ,n), i.e., lt_i is a diagonal matrix with tΛ O'? j ) diagonal element yt-i(j), j = 1,. . ,n. We consider optimal estimation for ^9, treating 7 as a nuisance parameter when a is known. We assume that ε* has a normal distribution for our illustration. Now
and Vt(y(t - 1),/?) = Ή.xZVαφlift-i,..
.,yi]ZYt-i
where X = (zi,..., x n ) and Z = (zi,..., z n ). To find the conditional expectation and variance, we derive the posterior density π(7|j/ί_i,... ,yi) of φ, conditional on the past observations
oc
p(yti,
r—\
(yr - Yr-^X'β + Z'Ί)) I exp j-Ifr'r-S - i (7 - ΔΓΛ^-ij'Δt-iίT - Δt-_\A-i) t-1 r=l XY
ΣU r-lVn{<x)-Xyr
r=l
- Σy'rVn{<*)-lYr-lX'β r=l
where ί-1
i K ί a ) - 1 ^ ! ^ + Γ"1 r=l
OPTIMAL ESTIMATING EQUATIONS and
265
ί-1 r=l
We then have βt(y(t — ί),β) and Vt(y(t — l),β) given by μt(y(t - 1),/3) = Yt-i{X'β + Z ' A ^ - i } , and - 1),/?) = Yt^
Vn(a).
Thus the optimal estimating equation for β is given as (5.1) and the optimal estimating function is computed as <Γ = t-\
where ί-1
Σ
—
A* Λ
t-ι —
r=l
and
BUi = Yt-iZ'A^ZYt-! + Vn(a). Hence, from the above equation, the optimal estimate of β is found as -.-1
τ ΓT
β =
Σ ,t=ι
Λ*
Ft*-1 A*
J
r=l
U=i
From (2.4), the information function corresponding to the optimal estimating function g* is obtained as
t=l
Suppose that, for fixed /?, we wish to estimate 7. We choose an elementary estimating function ht for 7 as
266
PARK AND BASAWA
Then the optimal estimating equation for 7 is given as (5.2) : 1
ι
Σ(r t _iZ')V n (α)- (yt - Yt-i(X'β + Z'Ί)) - T~ Ί = 0. t=l
Thus the above equation yields an estimate 7* of 7 when β is known. -1
T
= .t=i
•Σ The estimate 7* is optimal for 7 when β is known. When β is unknown, we replace it by β in 7* to obtain 7.
6
Concluding Remarks
In this paper, we have derived optimal estimating equations for estimating fixed and random parameters in mixed effects models with dependent observations. Among the issues that are not addressed in this paper are : (ϊ) asymptotic distribution theory, (ii) estimation of variance components, and (in) computational aspects. We hope to return to these topics in future work. Here, we content ourselves by offering the following remarks on these important issues. (i) Asymptotic Distribution Theory The consistency and asymptotic normality of the marginal quasi-likelihood estimate β in Section 5 can be established, under regularity conditions, from the general theory discussed by Heyde(1997). Appropriate extensions to develop asymptotic distribution theory for the joint estimation of β and 7 are needed. Moreover, work on asymptotic efficiency of the estimates will be useful. (ii) Estimation of Variance Components Assuming 7 ~ ΛΓ(0, Γ), one can estimate Γ from the marginal quasilikelihood in Section 5. An extension of the REML approach discussed by Breslow and Clayton(1993) can be used in practice. (in) Computational Aspects Extensions of Fisher scoring method discussed by Breslow and Clayton(1993) need to be developed. For most of the examples in our paper, however, we have obtained explicit solutions of the estimating equations. Consistent parameter estimates of the information matrices can easily be obtained and hence the estimates of the standard errors of the estimates can be computed, in principle.
OPTIMAL ESTIMATING EQUATIONS
267
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271 Institute of Mathematical Statistics LECTURE NOTES — MONOGRAPH SERIES
RECONSTRUCTION OF A STATIONARY SPATIAL PROCESS FROM A SYSTEMATIC