Gene by Sex Interaction for Measures of Obesity in the Framingham Heart Study

Abstract EN

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.