New loci for body fat percentage reveal link between adiposity and cardiometabolic disease risk.
New loci for body fat percentage reveal link between adiposity and cardiometabolic disease risk.
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DOI：
10.1038/ncomms10495
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发表时间：
2016-02-01
影响因子：
16.6
通讯作者：
Loos RJ
中科院分区：
文献类型：
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作者：
Lu Y;Day FR;Gustafsson S;Buchkovich ML;Na J;Bataille V;Cousminer DL;Dastani Z;Drong AW;Esko T;Evans DM;Falchi M;Feitosa MF;Ferreira T;Hedman ÅK;Haring R;Hysi PG;Iles MM;Justice AE;Kanoni S;Lagou V;Li R;Li X;Locke A;Lu C;Mägi R;Perry JR;Pers TH;Qi Q;Sanna M;Schmidt EM;Scott WR;Shungin D;Teumer A;Vinkhuyzen AA;Walker RW;Westra HJ;Zhang M;Zhang W;Zhao JH;Zhu Z;Afzal U;Ahluwalia TS;Bakker SJ;Bellis C;Bonnefond A;Borodulin K;Buchman AS;Cederholm T;Choh AC;Choi HJ;Curran JE;de Groot LC;De Jager PL;Dhonukshe-Rutten RA;Enneman AW;Eury E;Evans DS;Forsen T;Friedrich N;Fumeron F;Garcia ME;Gärtner S;Han BG;Havulinna AS;Hayward C;Hernandez D;Hillege H;Ittermann T;Kent JW;Kolcic I;Laatikainen T;Lahti J;Mateo Leach I;Lee CG;Lee JY;Liu T;Liu Y;Lobbens S;Loh M;Lyytikäinen LP;Medina-Gomez C;Michaëlsson K;Nalls MA;Nielson CM;Oozageer L;Pascoe L;Paternoster L;Polašek O;Ripatti S;Sarzynski MA;Shin CS;Narančić NS;Spira D;Srikanth P;Steinhagen-Thiessen E;Sung YJ;Swart KM;Taittonen L;Tanaka T;Tikkanen E;van der Velde N;van Schoor NM;Verweij N;Wright AF;Yu L;Zmuda JM;Eklund N;Forrester T;Grarup N;Jackson AU;Kristiansson K;Kuulasmaa T;Kuusisto J;Lichtner P;Luan J;Mahajan A;Männistö S;Palmer CD;Ried JS;Scott RA;Stancáková A;Wagner PJ;Demirkan A;Döring A;Gudnason V;Kiel DP;Kühnel B;Mangino M;Mcknight B;Menni C;O'Connell JR;Oostra BA;Shuldiner AR;Song K;Vandenput L;van Duijn CM;Vollenweider P;White CC;Boehnke M;Boettcher Y;Cooper RS;Forouhi NG;Gieger C;Grallert H;Hingorani A;Jørgensen T;Jousilahti P;Kivimaki M;Kumari M;Laakso M;Langenberg C;Linneberg A;Luke A;Mckenzie CA;Palotie A;Pedersen O;Peters A;Strauch K;Tayo BO;Wareham NJ;Bennett DA;Bertram L;Blangero J;Blüher M;Bouchard C;Campbell H;Cho NH;Cummings SR;Czerwinski SA;Demuth I;Eckardt R;Eriksson JG;Ferrucci L;Franco OH;Froguel P;Gansevoort RT;Hansen T;Harris TB;Hastie N;Heliövaara M;Hofman A;Jordan JM;Jula A;Kähönen M;Kajantie E;Knekt PB;Koskinen S;Kovacs P;Lehtimäki T;Lind L;Liu Y;Orwoll ES;Osmond C;Perola M;Pérusse L;Raitakari OT;Rankinen T;Rao DC;Rice TK;Rivadeneira F;Rudan I;Salomaa V;Sørensen TI;Stumvoll M;Tönjes A;Towne B;Tranah GJ;Tremblay A;Uitterlinden AG;van der Harst P;Vartiainen E;Viikari JS;Vitart V;Vohl MC;Völzke H;Walker M;Wallaschofski H;Wild S;Wilson JF;Yengo L;Bishop DT;Borecki IB;Chambers JC;Cupples LA;Dehghan A;Deloukas P;Fatemifar G;Fox C;Furey TS;Franke L;Han J;Hunter DJ;Karjalainen J;Karpe F;Kaplan RC;Kooner JS;McCarthy MI;Murabito JM;Morris AP;Bishop JA;North KE;Ohlsson C;Ong KK;Prokopenko I;Richards JB;Schadt EE;Spector TD;Widén E;Willer CJ;Yang J;Ingelsson E;Mohlke KL;Hirschhorn JN;Pospisilik JA;Zillikens MC;Lindgren C;Kilpeläinen TO;Loos RJ
为了增加我们对肥胖的遗传基础及其与心脏代谢疾病风险的联系的理解，我们对多达100，716人的体脂百分比（BF%）进行了全基因组关联荟萃分析。12个位点达到全基因组显著性（P<5 × 10−8），其中8个先前与总体肥胖（BMI，BF%）增加相关，4个（在COBLL 1/GRB 14，IGF 2BP 1，PLA 2G 6，CRTC 1中或附近）与BF%新关联。7个位点对BF%的影响大于对BMI的影响，提示与肥胖的主要关联，而5个位点对BMI的影响大于BF%，提示与脂肪和瘦体重的关联。特别是，与BF%更密切相关的基因座显示出不同的交叉表型关联特征，具有一系列心脏代谢特征，揭示了肥胖与疾病风险之间联系的新见解。 一项全基因组关联荟萃分析研究显示，新的遗传位点与体脂百分比相关，并描述了跨表型关联，进一步证明了肥胖与心血管疾病风险之间的密切关系。
To increase our understanding of the genetic basis of adiposity and its links to cardiometabolic disease risk, we conducted a genome-wide association meta-analysis of body fat percentage (BF%) in up to 100,716 individuals. Twelve loci reached genome-wide significance (P<5 × 10−8), of which eight were previously associated with increased overall adiposity (BMI, BF%) and four (in or near COBLL1/GRB14, IGF2BP1, PLA2G6, CRTC1) were novel associations with BF%. Seven loci showed a larger effect on BF% than on BMI, suggestive of a primary association with adiposity, while five loci showed larger effects on BMI than on BF%, suggesting association with both fat and lean mass. In particular, the loci more strongly associated with BF% showed distinct cross-phenotype association signatures with a range of cardiometabolic traits revealing new insights in the link between adiposity and disease risk. A genome-wide association meta-analysis study here shows novel genetic loci to be associated to body fat percentage, and describes cross-phenotype association that further demonstrate a close relationship between adiposity and cardiovascular disease risk.