title: Gene × dietary pattern interactions in obesity: analysis of up to 68 317 adults of European ancestry.
abstract: 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.
authors.affiliation: Division of Epidemiology, Human Genetics and Environmental Sciences, School of Public Health, University of Texas, Health Science Center, Houston, TX, USA.
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authors.affiliation: Jean Mayer USDA Human Nutrition Research Center on Aging, Friedman School of Nutrition Science and Policy, Tufts University, Boston, MA, USA.
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authors.affiliation: Department of Epidemiology, Erasmus MC, University Medical Center, Rotterdam, The Netherlands, Netherlands Genomics Initiative (NGI)-sponsored Netherlands Consortium for Healthy Aging (NCHA), Leiden, The Netherlands.
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authors.affiliation: Unit of Public Health Genomics, Institute for Molecular Medicine Finland (FIMM), University of Helsinki, Tukholmankatu 8, Helsinki 00290, Finland.
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authors.affiliation: Department of Nutrition and Dietetics, School of Health Science and Education, Harokopio University, Athens, Greece.
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authors.affiliation: The Genetics of Obesity and Related Metabolic Traits Program, The Charles Bronfman Institute for Personalized Medicine and The Mindich Child Health and Development Institute, The Icahn School of Medicine at Mount Sinai, New York, NY, USA.
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authors.affiliation: Department of Clinical Sciences, Genetic and Molecular Epidemiology Unit, Department of Nutrition, Harvard Chan School of Public Health, Boston, MA, USA, Department of Public Health and Clinical Medicine, Umeå University, Umeå, Sweden, paul.franks@med.lu.se.
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mesh_terms: D000328:Adult; D015992:Body Mass Index; D016022:Case-Control Studies; D066273:Diet, Western; D004843:Epistasis, Genetic; D005260:Female; D056426:Genetic Loci; D055106:Genome-Wide Association Study; D006801:Humans; D008297:Male; D009765:Obesity / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D044465:White People / Q000235:genetics*