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

Publication

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

Journal Paper/Review - May 20, 2015

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

Citation

Franks P, Uitterlinden A, Viikari J, Stirrups K, Hofman A, Barroso I, Perola M, Djoussé L, Kähönen M, Sjögren P, Deloukas P, van Rooij F, Jacobs D, Ericson U, Jula A, Hallmans G, Kalafati I, Franco O, Mozaffarian D, Loos R, Cupples L, Renström F, Lehtimäki T, Ingelsson E, Zillikens M, Orho-Melander M, Ferrucci L, Qi L, Dedoussis G, Eriksson J, Kritchevsky S, Knekt P, Borecki I, Salomaa V, Männistö S, Mukamal K, Raitakari O, Manichaikul A, Sonestedt E, Qi Q, Perälä M, Houston D, Nuotio M, Kristiansson K, Lemaitre R, Voortman T, Wojczynski M, Tanaka T, Ahmad S, Smith C, Ngwa J, Follis J, Kanoni S, Ganna A, Mikkilä V, Ax E, Dmitriou M, Booij L, Rich S, Rukh G, Bandinelli S, Hu F, Lahti J, Liu Y, Rissanen H, Johansson I, McKeown N, Harald K, Siscovick D, North K, Nettleton J. Gene × dietary pattern interactions in obesity: analysis of up to 68 317 adults of European ancestry. Hum Mol Genet 2015; 24:4728-38.

Type

Journal Paper/Review (English)

Journal

Hum Mol Genet 2015; 24

Publication Date

May 20, 2015

Issn Electronic

1460-2083

Pages

4728-38

Brief description/objective

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.