Recessive inheritance of obesity in familial non-insulin-dependent diabetes mellitus, and lack of linkage to nine candidate genes.

Segregation analysis of body-mass index (BMI) supported recessive inheritance of obesity, in pedigrees ascertained through siblings with non-insulin dependent diabetes mellitus (NIDDM). BMI was estimated as 39 kg/m2 for those subjects homozygous at the inferred locus. Two-locus segregation analysis provided weak support for a second recessive locus, with BMI estimated as 32 kg/m2 for homozygotes. NIDDM prevalence was increased among those subjects presumed to be homozygous at either locus. Using both parametric and nonparametric methods, we found no evidence of linkage of obesity to any of nine candidate genes/regions, including the Prader-Willi chromosomal region (PWS), the human homologue of the mouse agouti gene (ASP), and the genes for leptin (OB), the leptin receptor (OBR/DB), the beta3-adrenergic receptor (ADRB3), lipoprotein lipase (LPL), hepatic lipase (LIPC), glycogen synthase (GYS), and tumor necrosis factor alpha (TNFA).