RECESSIVE INHERITANCE OF OBESITY IN FAMILIAL NON-INSULIN-DEPENDENT DIABETES-MELLITUS, AND LACK OF LINKAGE TO 9 CANDIDATE GENES

Segregation analysis of body-mass index (BMI) supported recessive inhe ritance of obesity, in pedigrees ascertained through siblings with non -insulin dependent diabetes mellitus (NIDDM), BMI was estimated as 39 kg/m(2) for those subjects homozygous at the inferred locus. Two-locus segregation analysis provided weak support for a second recessive loc us, with BMI estimated as 32 kg/m(2) for homozygotes. NIDDM prevalence was increased among those subjects presumed to be homozygous at eithe r 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 homolo gue of the mouse agouti gene (ASP), and the genes for leptin (OB), the leptin receptor (OBR/DB), the beta(3)-adrenergic receptor (ADRB3), li poprotein lipase (LPL), hepatic lipase (LIPC), glycogen synthase (GYS) , and tumor necrosis factor alpha (TNFA).