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

Friday,2015-08-28 10:28 America/Los_Angeles — zdrager
TitleGene × dietary pattern interactions in obesity: analysis of up to 68 317 adults of European ancestry.
Publication TypeJournal Article
Year of Publication2015
AuthorsNettleton, 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, Sjogren, P, Kähönen, M, Djoussé, 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, CM, Ingelsson, E, Lehtimäki, T, Renstrom, F, Cupples, AL, Loos, RJF, Franks, PW
JournalHum Mol Genet
Volume24
Issue16
Pagination4728-38
Date Published2015 Aug 15
ISSN1460-2083
KeywordsAdult, Body Mass Index, Case-Control Studies, Diet, Western, Epistasis, Genetic, European Continental Ancestry Group, Female, Genetic Loci, Genome-Wide Association Study, Humans, Male, Obesity, Polymorphism, Single Nucleotide
Abstract<p>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.</p>
DOI10.1093/hmg/ddv186
Alternate JournalHum. Mol. Genet.
PubMed ID25994509
PubMed Central IDPMC4512626
Grant List089062/Z/09/Z / / Wellcome Trust / United Kingdom
263 MD 821336 / MD / NIMHD NIH HHS / United States
263 MD 9164 / MD / NIMHD NIH HHS / United States
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89061/Z/09/Z / / Wellcome Trust / United Kingdom
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