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

Abstract

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 non-parametric 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 β3- adrenergic receptor (ADRB3), lipoprotein lipase (LPL), hepatic lipase (LIPC), glycogen synthase (GYS), and tumor necrosis factor α (TNFA).