Gene × dietary pattern interactions in obesity: analysis of up to 68 317 adults of European ancestry.
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.
Nettleton, JA; Follis, JL; Ngwa, JS; Smith, CE; Ahmad, S; Tanaka, T; Wojczynski, MK; Voortman, T; Lemaitre, RN; Kristiansson, K; Nuotio, M-L; Houston, DK; Perälä, M-M; Qi, Q; Sonestedt, E; Manichaikul, A; Kanoni, S; Ganna, A; Mikkilä, V; North, KE; Siscovick, DS; Harald, K; Mckeown, NM; Johansson, I; Rissanen, H; Liu, Y; Lahti, J; Hu, FB; Bandinelli, S; Rukh, G; Rich, S; Booij, L; Dmitriou, M; Ax, E; Raitakari, O; Mukamal, K; Männistö, S; Hallmans, G; Jula, A; Ericson, U; Jacobs, DR; Van Rooij, FJA; Deloukas, P; Sjögren, P; Kähönen, M; Djousse, L; Perola, M; Barroso, I; Hofman, A; Stirrups, K; Viikari, J; Uitterlinden, AG; Kalafati, IP; Franco, OH; Mozaffarian, D; Salomaa, V; Borecki, IB; Knekt, P; Kritchevsky, SB; Eriksson, JG; Dedoussis, GV; Qi, L; Ferrucci, L; Orho-Melander, M; Zillikens, MC; Ingelsson, E; Lehtimäki, T; Renström, F; Cupples, LA; Loos, RJF; Franks, PW
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