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

Lookup NU author(s): Laura Pascoe

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This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).


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 x 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.


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Author(s): Lu YC, Day FR, Gustafsson S, Buchkovich ML, Na JB, Bataille V, Cousminer DL, Dastani Z, Drong AW, Esko T, Evans DM, Falchi M, Feitosa MF, Ferreira T, Hedman AK, Haring R, Hysi PG, Iles MM, Justice AE, Kanoni S, Lagou V, Li R, Li X, Locke A, Lu C, Magi R, Perry JRB, Pers TH, Qi QB, Sanna M, Schmidt EM, Scott WR, Shungin D, Teumer A, Vinkhuyzen AAE, Walker RW, Westra HJ, Zhang MF, Zhang WH, Zhao JH, Zhu ZH, Afzal U, Ahluwalia TS, Bakker SJL, Bellis C, Bonnefond A, Borodulin K, Buchman AS, Cederholm T, Choh AC, Choi HJ, Curran JE, de Groot LCPGM, De Jager PL, Dhonukshe-Rutten RAM, Enneman AW, Eury E, Evans DS, Forsen T, Friedrich N, Fumeron F, Garcia ME, Gartner S, Han BG, Havulinna AS, Hayward C, Hernandez D, Hillege H, Ittermann T, Kent JW, Kolcic I, Laatikainen T, Lahti J, Leach IM, Lee CG, Lee JY, Liu T, Liu YF, Lobbens S, Loh M, Lyytikainen LP, Medina-Gomez C, Michaelsson K, Nalls MA, Nielson CM, Oozageer L, Pascoe L, Paternoster L, Polasek O, Ripatti S, Sarzynski MA, Shin CS, Narancic NS, Spira D, Srikanth P, Steinhagen-Thiessen E, Sung YJ, Swart KMA, 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 JA, Mahajan A, Mannisto S, Palmer CD, Ried JS, Scott RA, Stancakova A, Wagner PJ, Demirkan A, Doring A, Gudnason V, Kiel DP, Kuhnel B, Mangino M, Mcknight B, Menni C, O'Connell JR, Oostra BA, Shuldiner AR, Song KJ, Vandenput L, van Duijn CM, Vollenweider P, White CC, Boehnke M, Boettcher Y, Cooper RS, Forouhi NG, Gieger C, Grallert H, Hingorani A, Jorgensen 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, Bluher 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, Heliovaara M, Hofman A, Jordan JM, Jula A, Kahonen M, Kajantie E, Knekt PB, Koskinen S, Kovacs P, Lehtimaki T, Lind L, Liu YM, Orwoll ES, Osmond C, Perola M, Perusse L, Raitakari OT, Rankinen T, Rao DC, Rice TK, Rivadeneira F, Rudan I, Salomaa V, Sorensen TIA, Stumvoll M, Tonjes A, Towne B, Tranah GJ, Tremblay A, Uitterlinden AG, van der Harst P, Vartiainen E, Viikari JS, Vitart V, Vohl MC, Volzke 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 JL, Hunter DJ, Karjalainen J, Karpe F, Kaplan RC, Kooner JS, McCarthy MI, Murabito JM, Morris AP, Bishop JAN, North KE, Ohlsson C, Ong KK, Prokopenko I, Richards JB, Schadt EE, Spector TD, Widen E, Willer CJ, Yang J, Ingelsson E, Mohlke KL, Hirschhorn JN, Pospisilik JA, Zillikens MC, Lindgren C, Kilpelainen TO, Loos RJF

Publication type: Article

Publication status: Published

Journal: Nature Communications

Year: 2016

Volume: 7

Print publication date: 01/02/2016

Online publication date: 01/02/2016

Acceptance date: 16/12/2015

Date deposited: 25/04/2016

ISSN (electronic): 2041-1723

Publisher: Nature Publishing Group

URL: http://dx.doi.org/10.1038/ncomms10495

DOI: 10.1038/ncomms10495


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