EPIGENOMICS AND METABOLOMICS MECHANISMS FOR A GENE X DIET INTERACTION MODULATING AGE-RELATED OBESITY

A functional variant in the apolipoprotein AII (APOA2) gene (rs5082) predisposes homozygous carriers to age-related obesity when habitual saturated fat (SFA) intake is high. We used epigenomics, transcription and metabolomics analyses to identify currently unknown mechanisms underlying this well-replicated gene x diet interaction. We conducted an epigenome-wide scan to compare genetically at-risk to low-risk individuals with low (<22 g/d) or high (≥22 g/d) SFA intake in the Boston Puerto Rican Health Study and validated the findings in the GOLDN Study and the Framingham Heart Study. In these three populations, we identified genotype-dependent differential methylation, only with high SFA int…