학술논문

Genome-wide physical activity interactions in adiposity - A meta-analysis of 200,452 adults.
Document Type
article
Author
Graff, MariaelisaScott, Robert AJustice, Anne EYoung, Kristin LFeitosa, Mary FBarata, LlildaWinkler, Thomas WChu, Audrey YMahajan, AnubhaHadley, DavidXue, LutingWorkalemahu, TsegaselassieHeard-Costa, Nancy Lden Hoed, MarcelAhluwalia, Tarunveer SQi, QibinNgwa, Julius SRenström, FridaQuaye, LydiaEicher, John DHayes, James ECornelis, MarilynKutalik, ZoltanLim, EliseLuan, Jian'anHuffman, Jennifer EZhang, WeihuaZhao, WeiGriffin, Paula JHaller, ToomasAhmad, ShafqatMarques-Vidal, Pedro MBien, StephanieYengo, LoicTeumer, AlexanderSmith, Albert VernonKumari, MeenaHarder, Marie NeergaardJustesen, Johanne MarieKleber, Marcus EHollensted, MetteLohman, KurtRivera, Natalia VWhitfield, John BZhao, Jing HuaStringham, Heather MLyytikäinen, Leo-PekkaHuppertz, CharlotteWillemsen, GonnekePeyrot, Wouter JWu, YingKristiansson, KatiDemirkan, AyseFornage, MyriamHassinen, MaijaBielak, Lawrence FCadby, GemmaTanaka, ToshikoMägi, Reedikvan der Most, Peter JJackson, Anne UBragg-Gresham, Jennifer LVitart, VeroniqueMarten, JonathanNavarro, PauBellis, ClairePasko, DorotaJohansson, ÅsaSnitker, SørenCheng, Yu-ChingEriksson, JoelLim, UnheeAadahl, MetteAdair, Linda SAmin, NajafBalkau, BeverleyAuvinen, JuhaBeilby, JohnBergman, Richard NBergmann, SvenBertoni, Alain GBlangero, JohnBonnefond, AmélieBonnycastle, Lori LBorja, Judith BBrage, SørenBusonero, FabioBuyske, SteveCampbell, HarryChines, Peter SCollins, Francis SCorre, TanguySmith, George DaveyDelgado, Graciela EDueker, NicoleDörr, MarcusEbeling, TapaniEiriksdottir, GudnyEsko, TõnuFaul, Jessica D
Source
PLoS genetics. 13(4)
Subject
CHARGE Consortium
EPIC-InterAct Consortium
PAGE Consortium
Humans
Obesity
Genetic Predisposition to Disease
Body Mass Index
Waist-Hip Ratio
Exercise
Genotype
Female
Male
Adiposity
Waist Circumference
Genome-Wide Association Study
Epigenomics
Alpha-Ketoglutarate-Dependent Dioxygenase FTO
Genetics
Developmental Biology
Language
Abstract
Physical activity (PA) may modify the genetic effects that give rise to increased risk of obesity. To identify adiposity loci whose effects are modified by PA, we performed genome-wide interaction meta-analyses of BMI and BMI-adjusted waist circumference and waist-hip ratio from up to 200,452 adults of European (n = 180,423) or other ancestry (n = 20,029). We standardized PA by categorizing it into a dichotomous variable where, on average, 23% of participants were categorized as inactive and 77% as physically active. While we replicate the interaction with PA for the strongest known obesity-risk locus in the FTO gene, of which the effect is attenuated by ~30% in physically active individuals compared to inactive individuals, we do not identify additional loci that are sensitive to PA. In additional genome-wide meta-analyses adjusting for PA and interaction with PA, we identify 11 novel adiposity loci, suggesting that accounting for PA or other environmental factors that contribute to variation in adiposity may facilitate gene discovery.