Nettleton JA, Follis JL, Ngwa JS, Smith CE, Ahmad S, Tanaka T, Wojczynski MK, Voortman T, Lemaitre RN, Kristiansson K, Nuotio ML, Houston DK, Perälä MM, 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 FJ, 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 RJ, Franks PW
Hum. Mol. Genet. 24 (16) 4728-4738 [2015-08-15; online 2015-05-20]
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.