Obesity is highly heritable. Genetic variants showing robust associations with obesity traits have been identified through genome-wide association studies. We investigated whether a composite score representing healthy diet modifies associations of these variants with obesity traits. Totally, 32 body mass index (BMI)- and 14 waist-hip ratio (WHR)-associated single nucleotide polymorphisms were genotyped, and genetic risk scores (GRS) were calculated in 18 cohorts of European ancestry (n = 68 317). Diet score was calculated based on self-reported intakes of whole grains, fish, fruits, vegetables, nuts/seeds (favorable) and red/processed meats, sweets, sugar-sweetened beverages and fried potatoes (unfavorable). Multivariable adjusted, linear regression within each cohort followed by inverse variance-weighted, fixed-effects meta-analysis was used to characterize: (a) associations of each GRS with BMI and BMI-adjusted WHR and (b) diet score modification of genetic associations with BMI and BMI-adjusted WHR. Nominally significant interactions (P = 0.006-0.04) were observed between the diet score and WHR-GRS (but not BMI-GRS), two WHR loci (GRB14 rs10195252; LYPLAL1 rs4846567) and two BMI loci (LRRN6C rs10968576; MTIF3 rs4771122), for the respective BMI-adjusted WHR or BMI outcomes. Although the magnitudes of these select interactions were small, our data indicated that associations between genetic predisposition and obesity traits were stronger with a healthier diet. Our findings generate interesting hypotheses; however, experimental and functional studies are needed to determine their clinical relevance.

dx.doi.org/10.1093/hmg/ddv186, hdl.handle.net/1765/85763
Human Molecular Genetics
This work was funded by the European Commission 7th Framework Programme; grant id fp7/261433 - Biobank Standardisation and Harmonisation for Research Excellence in the European Union (BIOSHARE-EU)
Department of Epidemiology

Nettleton, J.A, Follis, J.L, Ngwa, J.S, Smith, C.E, Ahmad, S, Tanaka, T, … Franks, P.W. (2015). Gene × dietary pattern interactions in obesity: Analysis of up to 68 317 adults of European ancestry. Human Molecular Genetics, 24(16), 4728–4738. doi:10.1093/hmg/ddv186