New loci for body fat percentage reveal link between adiposity and cardiometabolic disease risk.
Nature communications 2015 ; 7: 10495.
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, Polasek 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, Stančáková 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, 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
DOI : 10.1038/ncomms10495
PubMed ID : 26833246
PMCID : PMC4740398
URL : https://www.nature.com/articles/ncomms10495
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.