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

Jennifer A. Nettleton, Jack L. Follis, Julius S. Ngwa, Caren E. Smith, Shafqat Ahmad, Toshiko Tanaka, Mary K. Wojczynski, Trudy Voortman, Rozenn N. Lemaitre, Kati Kristiansson, Marja Liisa Nuotio, Denise K. Houston, Mia Maria Perälä, Qibin Qi, Emily Sonestedt, Ani Manichaikul, Stavroula Kanoni, Andrea Ganna, Vera Mikkilä, Kari E. NorthDavid S. Siscovick, Kennet Harald, Nicola M. Mckeown, Ingegerd Johansson, Harri Rissanen, Yongmei Liu, Jari Lahti, Frank B. Hu, Stefania Bandinelli, Gull Rukh, Stephen Rich, Lisanne Booij, Maria Dmitriou, Erika Ax, Olli Raitakari, Kenneth Mukamal, Satu Männistö, Göran Hallmans, Antti Jula, Ulrika Ericson, David R. Jacobs, Frank J. Frank, Panos Deloukas, Per Sjögren, Mika Kähönen, Luc Djousse, Markus Perola, Inês Barroso, Albert Hofman, Kathleen Stirrups, Jorma Viikari, André G. Uitterlinden, Ioanna P. Kalafati, Oscar H. Franco, Dariush Mozaffarian, Veikko Salomaa, Ingrid B. Borecki, Paul Knekt, Stephen B. Kritchevsky, Johan G. Eriksson, George V. Dedoussis, Lu Qi, Luigi Ferrucci, Marju Orho-Melander, M. Carola Zillikens, Erik Ingelsson, Terho Lehtimäki, Frida Renström, L. Adrienne Cupples, Ruth J.F. Loos, Paul W. Franks

Research output: Contribution to journalArticlepeer-review

80 Scopus citations


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.

Original languageEnglish
Pages (from-to)4728-4738
Number of pages11
JournalHuman molecular genetics
Issue number16
StatePublished - Apr 28 2015


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