The search for heterogeneity in insulin-dependent diabetes mellitus: evidence for familial and nonfamilial forms.

Using five different published sets of data, we looked at the distribution of HLA-DR genotypes among diabetic probands. It was possible to reject dominant inheritance at the HLA-associated locus, but some of the data were compatible with recessive inheritance while some were not. An attempt to reconcile the conflicting data by proposing a three-allele model apparently failed. It proved possible to resolve some of the conflicting data by proposing that simplex families represent primarily a recessive form of insulin dependent diabetes mellitus (IDDM) while multiplex families represent primarily two other subforms: one showing three-allele inheritance and one not. We also propose that the HLA locus involved in IDDM mediates the effect of an environmental agent on a second disease locus.