Detection of genetic heterogeneity between families of insulin-dependent diabetes mellitus patients using linkage analysis.

Much debate has taken place over the mode(s) of inheritance of insulin-dependent diabetes mellitus (IDDM) and the possibility of etiological heterogeneity. We have analyzed the disease status (IDDM) and genetic marker (HLA-A/B haplotype) data from 61 multiple-case IDDM families ascertained through two registries in the Pittsburgh, Pennsylvania, area. Linkage analysis results were similar for five previously published simple models of transmission. No heterogeneity could be detected on the basis of the total sample or when the sample was categorized according to the proband's HLA-B or HLA-DR type. In contrast, categorizing the families by generation(s) of the affected individuals revealed differences in the linkage analysis results. Families with affected siblings only (N = 38) showed strong evidence for close linkage for all models. Families with a parent and siblings affected (N = 6) showed evidence against close linkage between HLA-B and IDDM for some models.