Combined segregation and linkage analysis for IDDM and HLA-DR under several ascertainment assumptions

Combined segregation and linkage analysis of the Genetic Analysis Workshop 5 (GAW5) data suggests a complex basis for susceptibility to insulin-dependent diabetes mellitus (IDDM). One susceptibility gene, linked to the HLA-DR region, is additive on the liability scale (d = .49 +/- .15, t = 2.9 +/- .6) with a gene frequency q = .30 +/- .03. A second locus, with a gene frequency of q = .07 +/- .02, which is recessive and unlinked to HLA, is also suggested by the analysis. The ascertainment correction used has little effect on the results, presumably because most of the information comes from the cosegregation of HLA alleles and disease status. The results are consistent with a direct involvement of the HLA-DR region in susceptibility, but are not a proof of it.