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

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Abstract
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.