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.
Duke Institute for Genome Sciences and Policy, Duke University, Durham, NC 27708, USA.
Ashlee M
AM
Benjamin
Sunil
S
Suchindran
Kaela
K
Pearce
Jennifer
J
Rowell
Lillian F
LF
Lien
John R
JR
Guyton
Jeanette J
JJ
McCarthy
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