Stratification techniques to explore genotype environment interactions

Linkage analysis was performed on the GAW11 Problem 2 data set using strati fication to explore the effects of the environmental risk factors and the d ifferences between mild and severe phenotypes. Analysis of the four study p opulations stratified by the two risk factors identified regions on chromos omes 3 and 5 with significant evidence for linkage. Other loci were sought by removing families consistent with linkage to the chromosome 3 locus. Our studies identified a locus on chromosome 3 (markers 43-46) associated with the mild phenotype in the presence of risk factor 1 and with the severe ph enotype independent of risk factor 1. This suggests that distinct allelic v ariants at the chromosome 3 locus may cause different forms of disease. The locus identified on chromosome 5 (markers 36-39) was linked to the severe phenotype, but exposure to factor 1 or 2 may have a protective effect. The regions on chromosomes 3 and 5 appeared to have independent roles in diseas e etiology. Evidence for two loci on chromosome 1 linked to the mild form w as found. The methods successfully identified linkages and interaction cons istent with the generating model. (C) 1999 Wiley-Liss, Inc.