A generalized estimating equations approach to linkage analysis in sibships in relation to multiple markers and exposure factors

We describe a multiple regression approach to nonparametric linkage analysi s in sibships incorporating multiple genetic loci, environmental covariates , and interactions. The covariance in trait residuals between sib pairs is treated as the dependent variable, regressed upon identical-by-descent shar ing probabilities and interaction effects, using generalized estimating equ ations to allow for the correlations among multiple sib pairs within a sibs hip. Individual covariates can also be introduced in the model for the trai t means. An application to the GAW11 simulated data revealed linkage with e ach of the four simulated loci, as well as gene(x)environment interactions of E1 with loci C and D and gene(x)gene interactions among the cluster of l oci A, B, and D. (C) 1999 Wiley-Liss, Inc.