Gene x dietary pattern interactions in obesity: analysis of up to 68 317 adults of European ancestry

JA Nettleton, JL Follis, JS Ngwa, CE Smith, Shahzad Ahmad, T Tanaka, MK Wojczynski, Trudy Voortman, RN Lemaitre, K Kristiansson, ML Nuotio, DK Houston, MM Perala, QB Qi, E Sonestedt, A Manichaikul, S Kanoni, A Ganna, V Mikkila, KE NorthDS Siscovick, K Harald, NM McKeown, I Johansson, H Rissanen, YM Liu, J Lahti, FB Hu, S Bandinelli, G Rukh, S Rich, L Booij, M Dmitriou, E Ax, O Raitakari, K Mukamal, S Mannisto, G Hallmans, A Jula, U Ericson, DR Jacobs, FJA van Rooij, P Deloukas, P Sjogren, M Kahonen, L Djousse, M Perola, I Barroso, Bert Hofman, K Stirrups, J Viikari, André Uitterlinden, IP Kalafati, OH Franco Duran, D Mozaffarian, V Salomaa, IB Borecki, P Knekt, SB Kritchevsky, JG Eriksson, GV Dedoussis, L Qi, L Ferrucci, M Orho-Melander, M.C. Zillikens, E Ingelsson, T Lehtimaki, F Renstrom, LA Cupples, RJF Loos, PW Franks

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Obesity is highly heritable. Genetic variants showing robust associationswith 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 polymorphismswere 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-adjustedWHR 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-adjustedWHR 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.
Original languageUndefined/Unknown
Pages (from-to)4728-4738
Number of pages11
JournalHuman Molecular Genetics
Issue number16
Publication statusPublished - 2015

Research programs

  • EMC MM-01-39-09-A
  • EMC NIHES-01-64-02

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