Gene by sex interaction for measures of obesity in the Framingham Heart Study

Obesity is an increasingly prevalent and severe health concern with a substantial heritable component and marked sex differences. we sought to determine if the effect of genetic variants also differed by sex by performing a genome-wide association study modeling the effect of genotype-by-sex interaction on obesity phenotypes. genotype data from individuals in the framingham heart study offspring cohort were analyzed across five exams. although no variants showed genome-wide significant gene-by-sex interaction in any individual exam,four polymorphisms displayed a consistent bmi association (p-values.00186 to.00010) across all five exams. these variants were clustered downstream of lyplal1,which encodes a lipase/esterase expressed in adipose tissue,a locus previously identified as having sex-specific effects on central obesity. primary effects in males were in the opposite direction from females and were replicated in framingham generation 3. our data support a sex-influenced association between genetic variation at the lyplal1 locus and obesity-related traits. © 2011 ashlee m. benjamin et al.