New loci for body fat percentage reveal link between adiposity and cardiometabolic disease risk

Yingchang Lu,F. Day,S. Gustafsson,S. Gustafsson,Martin L. Buchkovich,Jianbo Na,Veronique Bataille,Veronique Bataille,D. Cousminer,Z. Dastani,A. Drong,T. Esko,David M. Evans,Mario Falchi,Mario Falchi,M. Feitosa,T. Ferreira,Å. Hedman,R. Haring,P. Hysi,M. Iles,A. Justice,S. Kanoni,S. Kanoni,V. Lagou,V. Lagou,Rui Li,Xin Li,A. Locke,Chen Lu,R. Mägi,J. Perry,T. Pers,Q. Qi,M. Sanna,M. Sanna,Ellen M. Schmidt,W. Scott,W. Scott,Dmitry Shungin,Dmitry Shungin,A. Teumer,Anna A. E. Vinkhuyzen,Ryan W. Walker,H. Westra,H. Westra,Mingfeng Zhang,Weihua Zhang,Weihua Zhang,J. Zhao,Zhihong Zhu,U. Afzal,U. Afzal,T. Ahluwalia,S. Bakker,C. Bellis,A. Bonnefond,A. Bonnefond,K. Borodulin,A. Buchman,T. Cederholm,A. Choh,H. Choi,J. Curran,L. Groot,P. Jager,P. Jager,P. Jager,R. Dhonukshe-Rutten,A. Enneman,Elodie Eury,Elodie Eury,Daniel S. Evans,T. Forsén,N. Friedrich,F. Fumeron,M. Garcia,Simone Gartner,B. Han,A. Havulinna,C. Hayward,D. Hernandez,H. Hillege,T. Ittermann,J. Kent,I. Kolčić,T. Laatikainen,T. Laatikainen,J. Lahti,I. Leach,Christine G. Lee,Jong-Young Lee,Tian Liu,Youfang Liu,S. Lobbens,S. Lobbens,Marie Loh,Marie Loh,L. Lyytikäinen,C. Medina-Gomez,K. Michaëlsson,M. Nalls,C. Nielson,Laticia Oozageer,L. Pascoe,L. Paternoster,O. Polašek,O. Polašek,S. Ripatti,S. Ripatti,M. Sarzynski,C. Shin,N. S. Narančić,D. Spira,P. Srikanth,E. Steinhagen-Thiessen,Y. Sung,K. Swart,K. Swart,L. Taittonen,Toshiko Tanaka,E. Tikkanen,N. Velde,N. M. Schoor,N. M. Schoor,N. Verweij,A. Wright,Lei Yu,J. Zmuda,N. Eklund,T. Forrester,N. Grarup,A. Jackson,K. Kristiansson,K. Kristiansson,T. Kuulasmaa,J. Kuusisto,P. Lichtner,J. Luan,A. Mahajan,S. Männistö,Cameron D. Palmer,Cameron D. Palmer,J. Ried,R. Scott,A. Stančáková,Peter J Wagner,Peter J Wagner,A. Demirkan,A. Döring,V. Gudnason,D. Kiel,Brigitte Kühnel,M. Mangino,B. McKnight,B. McKnight,C. Menni,J. O’Connell,B. Oostra,A. Shuldiner,Kijoung Song,L. Vandenput,C. Duijn,P. Vollenweider,Charles White,M. Boehnke,Y. Boettcher,R. Cooper,N. Forouhi,C. Gieger,H. Grallert,A. Hingorani,T. Jørgensen,T. Jørgensen,P. Jousilahti,M. Kivimäki,M. Kumari,M. Laakso,C. Langenberg,A. Linneberg,A. Luke,C. McKenzie,A. Palotie,A. Palotie,A. Palotie,O. Pedersen,A. Peters,K. Strauch,B. Tayo,N. Wareham,D. Bennett,Lars Bertram,Lars Bertram,J. Blangero,M. Blüher,C. Bouchard,H. Campbell,N. Cho,S. Cummings,S. Czerwinski,I. Demuth,R. Eckardt,Johan G. Eriksson,Johan G. Eriksson,L. Ferrucci,O. Franco,P. Froguel,P. Froguel,R. Gansevoort,T. Hansen,T. Hansen,T. Harris,N. Hastie,M. Heliövaara,A. Hofman,J. Jordan,A. Jula,M. Kähönen,E. Kajantie,E. Kajantie,E. Kajantie,P. Knekt,S. Koskinen,P. Kovacs,T. Lehtimäki,L. Lind,Yongmei Liu,E. Orwoll,C. Osmond,M. Perola,M. Perola,L. Pérusse,Olli T Raitakari,Olli T Raitakari,T. Rankinen,D. Rao,T. Rice,F. Rivadeneira,I. Rudan,V. Salomaa,T. Sørensen,M. Stumvoll,A. Tönjes,B. Towne,G. Tranah,A. Tremblay,A. Uitterlinden,P. Harst,E. Vartiainen,J. Viikari,V. Vitart,M. Vohl,H. Völzke,Mark Walker,Mark Walker,H. Wallaschofski,S. Wild,James F. Wilson,L. Yengo,L. Yengo,D. Bishop,I. Borecki,I. Borecki,J. Chambers,J. Chambers,J. Chambers,L. Cupples,A. Dehghan,P. Deloukas,P. Deloukas,P. Deloukas,G. Fatemifar,C. Fox,T. Furey,L. Franke,Jiali Han,D. Hunter,J. Karjalainen,F. Karpe,R. Kaplan,J. Kooner,J. Kooner,J. Kooner,M. McCarthy,J. Murabito,A. P. Morris,A. P. Morris,J. N. Bishop,K. North,C. Ohlsson,K. Ong,I. Prokopenko,J. B. Richards,E. Schadt,T. Spector,E. Widén,C. Willer,Jian Yang,E. Ingelsson,E. Ingelsson,E. Ingelsson,K. Mohlke,Joel N. Hirschhorn,Joel N. Hirschhorn,Joel N. Hirschhorn,J. Pospisilik,M. Zillikens,C. Lindgren,T. Kilpeläinen,T. Kilpeläinen,R. Loos

Published 2016 in Nature Communications

ABSTRACT

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.

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