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Peter Dalgaard

Department of Biostatistics University of Copenhagen

Mixed Models in R, January 2006

lme

Department of Biostatistics University of Copenhagen

Introduction

lme is the predecessor of lmer It has a more complicated syntax, and is not quite as fast But it is also more stable . . . and will ﬁt some models that lmer can not ﬁt

lme

Department of Biostatistics University of Copenhagen

Overview

Basic model Some simple examples Grouped data classes Rudimentary Lattice (Trellis) graphics Specifying random components

lme

Department of Biostatistics University of Copenhagen

. Ψ). . . M ∼ N(0.Model Laird and Ware (1982): yi = Xi β + Zi bi + bi ∼ N(0. σ 2 I) β ﬁxed effects (p-vector) bi random effects (q-vectors) Xi matrix (ni × p) Zi matrix (ni × q) lme Department of Biostatistics University of Copenhagen . i i i = 1. .

Ψ2 ). . bij ∼ N(0. . Mi i ∼ N(0.j matrix (nij × q1 ) (Notice the comma!) Zij matrix (nij × q2 ) Extends to more than two levels lme Department of Biostatistics University of Copenhagen . . σ 2 I) bi level-1 random effects (q1 -vectors) bij level-2 random effects (q2 -vectors) Zi. . ij j = 1. . M bi ∼ N(0. . .j bi + Zij bij + i = 1. Ψ1 ). .Multilevel extension Pinheiro and Bates use the following notation yij = Xij β + Zi.

Basic usage library(nlme) data(Rail) lset(col.random=~1|Rail) lme Department of Biostatistics University of Copenhagen .data=Rail.whitebg()) plot(Rail) lme(travel~1.

Remarks Standard one-way ANOVA with random variation Variation between rails larger than expected from variation within same rail Notice speciﬁcation random=~1|Rail The DF calculation is not quite right. lme Department of Biostatistics University of Copenhagen .

Grouped Data objects The Rail object is a generalized data frame encoding the grouping of data That’s why it works just to say plot(Rail) Default formulas can use this information. lme(travel 1.data=Rail) or even lme(Rail) would sufﬁce lme Department of Biostatistics University of Copenhagen .

)~fitted(.resid(.)|Rail) These plots are made by lattice (Trellis) using xyplot Considerable freedom in choice of display lme Department of Biostatistics University of Copenhagen .data=Rail) plot(r1) plot(r1.lme(travel~1.Plotting residuals r1 <.

data=Rail. Here.ML versus REML lme(travel~1. only the estimate for Rail effect is biased lme Department of Biostatistics University of Copenhagen .method="ML") ML estimators generally biased downwards.

but allows you to specify error model variance functions (weights argument) correlation structure (correlation argument) Similar syntax applies to lme() lme Department of Biostatistics University of Copenhagen .The gls function Like lm.

power function) Can depend on parameters and covariates Possibly have different parameters for different groups Basic syntax varPower(form=~age|sex) age is the variance covariate sex is a grouping (separate parameters per group) Special covariate fitted(.Variance function classes Describe functional dependence (e.) lme Department of Biostatistics University of Copenhagen .g.

Precooked variance function classes Notice: varPower() creates an object of class "varPower" inheriting from "varFunc" gnls “knows” how to use such objects and associated methods to ﬁt the model Relevant help page: varClasses Currently varExp. varComb Notice that they work on standard deviation scale (somewhat counterintuitively) lme Department of Biostatistics University of Copenhagen . varFixed. varIdent. varPower. varConstPower.

but there are actually not many lines to modify lme Department of Biostatistics University of Copenhagen .Writing your own The internal structure of a variance function object is a parameter vector with a bunch of attributes You’ll need to change the calculation of the "weights" and "logLike" attributes Modify the functions for an existing class. varPower The functions are fairly complex.g. e.

corRatio. corExp. corLin. . .C() calls inside. The | symbol now means “within group” For help. ) lme Department of Biostatistics University of Copenhagen .Correlation structures Much the same story as variance functions There can be (multiple) covariate dependencies. corCAR1. corGaus. so not too attractive to write your own (but you could. corSymm The functions tend to have . look at corClasses corAR1. corCompSymm. corARMA. typically deﬁning spatial coordinates/distances. corSpher.

Trying to use lme just leads to confusion lme Department of Biostatistics University of Copenhagen .Example Let us consider the spinal BMD example from yesterday To get an unrestricted covariance matrix within subject we need to use an unrestricted correlations structure (corSymm) and a variance that depends on time Notice that we need to use gls.

direction="long") library(lattice) spiLong$time2 <..Demo 1 library(nlme) spi <. groups=grp.c(0. correlation=corSymm(form=~time|id).names="spinebmd". varying=list(names(spi)[2:8]).csv") spiLong <. type="l".reshape(spi. weight=varIdent(form=~1|time)) summary(m1) lme Department of Biostatistics University of Copenhagen ..6.gls(spinebmd~time2+grp:time2.omit(spiLong). v.read.factor(spiLong$grp) xyplot(spinebmd~time2|id.omit(spiLong)) #this takes a while.3.24)[spiLong$time] spiLong$grp <. data=na.csv("spinebmd.18.12. m1 <. data=na.9.

let us compare the unrestricted model with a random coefﬁcient regression m2 <.m2) summary(m2) lme Department of Biostatistics University of Copenhagen . data=na..omit(spiLong)) anova(m1. random=~time2|id.Comparisons between gls and lme models Models from the two functions can be compared trivially.g.lme(fixed=spinebmd~time2+grp:time2. using anova E.

Ψ = τ 2 I. i.e. data=Rail) Using one creates a grouping with only one group Notice that we now specify random terms as a list of objects per grouping level Random effects have covariance structure according to pdIdent.nrow(Rail)) lme(travel~1.random=list(one=pdIdent(~Rail-1)).Patterned covariance matrices for random effects Back with lme consider an alternative way of specifying a Rail effect: one <. lme Department of Biostatistics University of Copenhagen .rep(1. It is important to use the -1 in the formula.

with no additional structure pdDiag: diagonal pdIdent: multiple of an identity pdCompSymm: compound symmetry structure (constant diagonal and constant off-diagonal elements) pdBlocked: block-diagonal matrix. with diagonal blocks of any "atomic" ‘pdMat’ class Roll your own (rather hard work: each class has 10–17 methods!) lme Department of Biostatistics University of Copenhagen .The pdMat classes pdSymm: general positive-deﬁnite matrix.

g.data=Rail.weights=varIdent(form=~1|Rail)) lme Department of Biostatistics University of Copenhagen . you can have different variances in each group lme(travel~1.Extended residual variances The same error modeling techniques as for gls models are available E.

subset(Orthodont. Sex=="Female") plot(OrthoFem) plot(intervals(lmList(distance ~ age. data=OrthoFem))) Now there’s a covariate age involved lmList calculates individual regression lines Notice that the intercepts are not really informative lme Department of Biostatistics University of Copenhagen .Another example data(Orthodont) OrthoFem <.

lme(distance ~ age.of2) Compare random intercept model to random line model Likelihood ratio test (on 2 DF) lme Department of Biostatistics University of Copenhagen . random=~1|Subject) of2 <. data=OrthoFem. data=OrthoFem.Comparing models of1 <.lme(distance ~ age. random=~age|Subject) anova(of1.

lme Department of Biostatistics University of Copenhagen . aspect="xy" tries to make average slope 45◦ to horisontal Notice how lines are biased towards central slope. aspect="xy") The function augPred augments the model with predicted values Plotting an augPred object overlays ﬁtted curves on data.Plotting results plot(augPred(of2). (grid=TRUE plots grey grid. grid=TRUE.

) needed in R A 3rd form of random effects: List of formulas Fitted curves are parabolic Curvature is constant Sides of same dog: vertical displacement Different dogs may have peaks in different places lme Department of Biostatistics University of Copenhagen . random=list(Dog=~day.lme(pixel~day+I(day^2).A two-level model data(Pixel) px1 <. data=Pixel.Side=~1)) plot(augPred(px1)) Notice S/R difference: I(.

update(px1.update(px1.px3) Cannot eliminate random effect of Side Cannot assume all peaks at same position lme Department of Biostatistics University of Copenhagen .random=~1|Dog/Side) anova(px1.Modifying the random structure px2 <.px2) px3 <.random=~day|Dog) anova(px1.

+Side) summary(px4) anova(px4) px1ml <.fixed=~.px4ml) Note necessary to extend ﬁxed part of model with Side term No systematic effect of side Likelihood tests between models do not work with REML lme Department of Biostatistics University of Copenhagen .method="ML") anova(px1ml.update(px4.update(px1.update(px1.Comparing ﬁxed terms px4 <.method="ML") px4ml <.

Crossed random effcts lme generally assumes nested random effects I.g.. no particular between person 1 in group 1 and person 1 in group 2 However. measurements made with p bloodﬂow probes simultaneously at n times There can be both correlations between measurements at the same time and between measurements with the same probe lme Department of Biostatistics University of Copenhagen .e. crossed effects can be relevant E.

pdIdent(~sample-1). but not all of it (independent blocks a re retained) lme Department of Biostatistics University of Copenhagen .lme(logDens~sample*dilut. data=Assay. pdIdent(~dilut-1)))) Notice that we must again use ~sample-1 to “trick” R into generating incidence matrices rather than contrast matrices You lose some of the multilevel structure this way.Coding crossed effects data(Assay) as1 <. random=pdBlocked(list( pdIdent(~1).

Block=pdIdent(~sample-1). lme Department of Biostatistics University of Copenhagen .lme(logDens~sample*dilut.lme(logDens~sample*dilut.Alternate forms as2 <. pdIdent(~sample-1))). random=list(Block=pdBlocked(list( pdIdent(~1).dilut=~1)) as3 <. data=Assay. dilut=~1)) None of them gets DF quite right though. random=list(Block=~1. data=Assay. . .

A Growth Curve Example Susanne Kjærgaard collected these data on children with CDG (Congenital Deﬁciency of Glycosylation) This disease causes severe growth retardation Purpose: Reference curves Mean value modeled using spline curve Random part as random coefﬁcient regression + autoregression Digging out the relevant part of the model object to ﬁnd the covariance of the random regression terms was a bit tricky lme Department of Biostatistics University of Copenhagen .

mat %*% x}) +lme. correlation=corExp(form=~sqrt(Age).obj$sigma^2 * as.new <.5.obj$modelStruct$reStruct$ID) SD <.5)). knots=sqrt(c(0. random=~sqrt(Age)|ID.knots=sqrt(c(0.mat <..Outline of analysis (Some plotting code omitted) lme.lme(log(Height)~ns(sqrt(Age).0. function(a){x<-c(1.sqrt(a)).obj$sigma^2) lme Department of Biostatistics University of Copenhagen .seq(0.obj <. t(x) %*% C.new. Boundary.10))).nugget=F)) Age.lme.10.1.sqrt(sapply(Age.matrix(lme.01) C.25.

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