Genome-wide physical activity interactions in adiposity - A meta-analysis of 200,452 adults.
Genome-wide physical activity interactions in adiposity - A meta-analysis of 200,452 adults.
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DOI：
10.1371/journal.pgen.1006528
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发表时间：
2017-04
期刊：
影响因子：
4.5
通讯作者：
Kilpeläinen TO
中科院分区：
文献类型：
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作者：
Graff M;Scott RA;Justice AE;Young KL;Feitosa MF;Barata L;Winkler TW;Chu AY;Mahajan A;Hadley D;Xue L;Workalemahu T;Heard-Costa NL;den Hoed M;Ahluwalia TS;Qi Q;Ngwa JS;Renström F;Quaye L;Eicher JD;Hayes JE;Cornelis M;Kutalik Z;Lim E;Luan J;Huffman JE;Zhang W;Zhao W;Griffin PJ;Haller T;Ahmad S;Marques-Vidal PM;Bien S;Yengo L;Teumer A;Smith AV;Kumari M;Harder MN;Justesen JM;Kleber ME;Hollensted M;Lohman K;Rivera NV;Whitfield JB;Zhao JH;Stringham HM;Lyytikäinen LP;Huppertz C;Willemsen G;Peyrot WJ;Wu Y;Kristiansson K;Demirkan A;Fornage M;Hassinen M;Bielak LF;Cadby G;Tanaka T;Mägi R;van der Most PJ;Jackson AU;Bragg-Gresham JL;Vitart V;Marten J;Navarro P;Bellis C;Pasko D;Johansson Å;Snitker S;Cheng YC;Eriksson J;Lim U;Aadahl M;Adair LS;Amin N;Balkau B;Auvinen J;Beilby J;Bergman RN;Bergmann S;Bertoni AG;Blangero J;Bonnefond A;Bonnycastle LL;Borja JB;Brage S;Busonero F;Buyske S;Campbell H;Chines PS;Collins FS;Corre T;Smith GD;Delgado GE;Dueker N;Dörr M;Ebeling T;Eiriksdottir G;Esko T;Faul JD;Fu M;Færch K;Gieger C;Gläser S;Gong J;Gordon-Larsen P;Grallert H;Grammer TB;Grarup N;van Grootheest G;Harald K;Hastie ND;Havulinna AS;Hernandez D;Hindorff L;Hocking LJ;Holmens OL;Holzapfel C;Hottenga JJ;Huang J;Huang T;Hui J;Huth C;Hutri-Kähönen N;James AL;Jansson JO;Jhun MA;Juonala M;Kinnunen L;Koistinen HA;Kolcic I;Komulainen P;Kuusisto J;Kvaløy K;Kähönen M;Lakka TA;Launer LJ;Lehne B;Lindgren CM;Lorentzon M;Luben R;Marre M;Milaneschi Y;Monda KL;Montgomery GW;De Moor MHM;Mulas A;Müller-Nurasyid M;Musk AW;Männikkö R;Männistö S;Narisu N;Nauck M;Nettleton JA;Nolte IM;Oldehinkel AJ;Olden M;Ong KK;Padmanabhan S;Paternoster L;Perez J;Perola M;Peters A;Peters U;Peyser PA;Prokopenko I;Puolijoki H;Raitakari OT;Rankinen T;Rasmussen-Torvik LJ;Rawal R;Ridker PM;Rose LM;Rudan I;Sarti C;Sarzynski MA;Savonen K;Scott WR;Sanna S;Shuldiner AR;Sidney S;Silbernagel G;Smith BH;Smith JA;Snieder H;Stančáková A;Sternfeld B;Swift AJ;Tammelin T;Tan ST;Thorand B;Thuillier D;Vandenput L;Vestergaard H;van Vliet-Ostaptchouk JV;Vohl MC;Völker U;Waeber G;Walker M;Wild S;Wong A;Wright AF;Zillikens MC;Zubair N;Haiman CA;Lemarchand L;Gyllensten U;Ohlsson C;Hofman A;Rivadeneira F;Uitterlinden AG;Pérusse L;Wilson JF;Hayward C;Polasek O;Cucca F;Hveem K;Hartman CA;Tönjes A;Bandinelli S;Palmer LJ;Kardia SLR;Rauramaa R;Sørensen TIA;Tuomilehto J;Salomaa V;Penninx BWJH;de Geus EJC;Boomsma DI;Lehtimäki T;Mangino M;Laakso M;Bouchard C;Martin NG;Kuh D;Liu Y;Linneberg A;März W;Strauch K;Kivimäki M;Harris TB;Gudnason V;Völzke H;Qi L;Järvelin MR;Chambers JC;Kooner JS;Froguel P;Kooperberg C;Vollenweider P;Hallmans G;Hansen T;Pedersen O;Metspalu A;Wareham NJ;Langenberg C;Weir DR;Porteous DJ;Boerwinkle E;Chasman DI;CHARGE Consortium;EPIC-InterAct Consortium;PAGE Consortium;Abecasis GR;Barroso I;McCarthy MI;Frayling TM;O'Connell JR;van Duijn CM;Boehnke M;Heid IM;Mohlke KL;Strachan DP;Fox CS;Liu CT;Hirschhorn JN;Klein RJ;Johnson AD;Borecki IB;Franks PW;North KE;Cupples LA;Loos RJF;Kilpeläinen TO
体力活动（PA）可能会改变导致肥胖风险增加的遗传效应。为了确定 PA 影响的肥胖位点，我们对 200,452 名欧洲（n = 180,423）或其他血统（n = 20,029）成年人的 BMI 和 BMI 调整后的腰围和腰臀比进行了全基因组相互作用荟萃分析。我们通过将 PA 分类为二分变量来对其进行标准化，其中平均 23% 的参与者被归类为不活跃，77% 的参与者被归类为活跃。虽然我们复制了 FTO 基因中已知最强的肥胖风险位点与 PA 的相互作用，与不活动的个体相比，其影响在体力活动个体中减弱约 30%，但我们没有识别出对 PA 敏感的其他位点。在调整 PA 和与 PA 相互作用的其他全基因组荟萃分析中，我们确定了 11 个新的肥胖基因座，这表明考虑 PA 或其他导致肥胖变异的环境因素可能有助于基因发现。日常体力活动的减少被认为是全球肥胖流行的一个关键因素。然而，久坐对肥胖的影响可能部分取决于一个人的遗传体质。对体力活动敏感并调节肥胖的特定基因变异仍然很大程度上未知。在这里，我们的目的是通过检查多达 200,452 个人的约 250 万个遗传变异，来识别对肥胖的影响会因体力活动而改变的遗传变异。 We also tested whether adjusting for physical activity as a covariate could lead to the identification of novel adiposity variants.我们发现了 FTO 基因中已知最强的肥胖风险位点与体力活动相互作用的有力证据，与不活动的个体相比，体力活动个体的体重指数增加效应减弱约 30%。我们的分析表明可能存在其他类似的基因-身体活动相互作用，但需要更好地测量身体活动、更大的样本量和/或改进的分析方法来识别它们。根据体力活动进行调整，我们发现了 11 种新的肥胖变异，这表明考虑体力活动或其他导致肥胖变异的环境因素可能有助于基因发现。
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. Decline in daily physical activity is thought to be a key contributor to the global obesity epidemic. However, the impact of sedentariness on adiposity may be in part determined by a person’s genetic constitution. The specific genetic variants that are sensitive to physical activity and regulate adiposity remain largely unknown. Here, we aimed to identify genetic variants whose effects on adiposity are modified by physical activity by examining ~2.5 million genetic variants in up to 200,452 individuals. We also tested whether adjusting for physical activity as a covariate could lead to the identification of novel adiposity variants. We find robust evidence of interaction with physical activity for the strongest known obesity risk-locus in the FTO gene, of which the body mass index-increasing effect is attenuated by ~30% in physically active individuals compared to inactive individuals. Our analyses indicate that other similar gene-physical activity interactions may exist, but better measurement of physical activity, larger sample sizes, and/or improved analytical methods will be required to identify them. Adjusting for physical activity, we identify 11 novel adiposity variants, suggesting that accounting for physical activity or other environmental factors that contribute to variation in adiposity may facilitate gene discovery.