Gene×dietary pattern interactions in obesity: analysis of up to 68,317 adults of European ancestry.
Author
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Jennifer A Nettleton
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Jack L Follis
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Julius S Ngwa
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Caren E Smith
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Shafqat Ahmad
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Toshiko Tanaka
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Mary K Wojczynski
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Trudy Voortman
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Rozenn N Lemaitre
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Kati Kristiansson
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Marja-Liisa Nuotio
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Denise K Houston
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Mia-Maria Perälä
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Qibin Qi
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Emily Sonestedt
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Ani Manichaikul
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Stavroula Kanoni
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Andrea Ganna
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Vera Mikkilä
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Kari E North
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David S Siscovick
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Kennet Harald
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Nicola M McKeown
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Ingegerd Johansson
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Harri Rissanen
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Yongmei Liu
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Jari Lahti
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Frank B Hu
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Stefania Bandinelli
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Gull Rukh
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Stephen Rich
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Lisanne Booij
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Maria Dmitriou
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Erika Ax
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Olli Raitakari
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Kenneth Mukamal
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Satu Männistö
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Göran Hallmans
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Antti Jula
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Ulrika Ericson
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David R Jacobs
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Frank J A van Rooij
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Panos Deloukas
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Per Sjögren
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Mika Kähönen
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Luc Djousse
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Markus Perola
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Inês Barroso
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Albert Hofman
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Kathleen Stirrups
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Jorma Viikari
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André G Uitterlinden
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Ioanna P Kalafati
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Oscar H Franco
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Dariush Mozaffarian
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Veikko Salomaa
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Ingrid B Borecki
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Paul Knekt
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Stephen B Kritchevsky
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Johan G Eriksson
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George V Dedoussis
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Lu Qi
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Luigi Ferrucci
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Marju Orho-Melander
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M Carola Zillikens
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Erik Ingelsson
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Terho Lehtimäki
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Frida Renström
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L Adrienne Cupples
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Ruth Loos
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Paul Franks
Summary, in English
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. 32 BMI- and 14 waist-hip ratio (WHR)-associated SNPs were genotyped and genetic risk scores (GRS) 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, fried potatoes (unfavorable). Multi-variable 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; 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.