Association and linkage for age at onset of a common oligogenic disease using genetic variance component models

The aims of our analysis were: (1) to investigate association of single nuc leotide polymorphisms (SNPs) and other covariates with age at onset in the simulated Genetic Analysis Workshop (GAW) 12 general population data, and ( 2) to use the polygenic random effects estimated during model fitting (sigm a squared A random effects) as input to a Haseman-Elston linkage analysis. The association analyses used genetic variance component models in a genera lized linear mixed models framework and were fitted using Gibbs sampling. T his method successfully detected the only three sequenced genes that were a lso major genes. The single-point linkage analysis used all markers provide d. Regions of linkage were found close to all four of the sites of major ge nes that explained a non-trivial component of the variance of age at onset. In all four cases the linkage peak fell within 5 cM of the true location. In three cases the peak significance was p < 0.01. (C) 2001 Wiley-Liss, Inc .