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 nucleotide 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 (sigma squared A random effects) as input to a Haseman-Elston linkage analysis. The association analyses used genetic variance component models in a generalized linear mixed models framework and were fitted using Gibbs sampling. This method successfully detected the only three sequenced genes that were also major genes. The single-point linkage analysis used all markers provided. Regions of linkage were found close to all four of the sites of major genes 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.