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

YC Lu, FR Day, S Gustafsson, ML Buchkovich, JB Na, V Bataille, DL Cousminer, Z Dastani, AW Drong, T Esko, DM Evans, M Falchi, MF Feitosa, T Ferreira, AK Hedman, R Haring, PG Hysi, MM Iles, AE Justice, S KanoniV Lagou, R Li, X Li, A Locke, C Lu, R Magi, JRB Perry, TH Pers, QB Qi, M Sanna, EM Schmidt, WR Scott, D Shungin, A Teumer, AAE Vinkhuyzen, RW Walker, HJ Westra, MF Zhang, WH Zhang, JH Zhao, ZH Zhu, U Afzal, TS Ahluwalia, SJL Bakker, C Bellis, A Bonnefond, K Borodulin, AS Buchman, T Cederholm, AC Choh, HJ Choi, JE Curran, LCPGM (Lisette) de Groot, PL De Jager, RAM Dhonukshe-Rutten, Anke Enneman, E Eury, DS Evans, T Forsen, N Friedrich, F Fumeron, ME Garcia, S Gartner, BG Han, AS Havulinna, C Hayward, D Hernandez, H Hillege, T Ittermann, JW Kent, I Kolcic, T Laatikainen, J Lahti, IM Leach, CG Lee, JY Lee, T Liu, YF Liu, S Lobbens, M Loh, LP Lyytikainen, C Medina-Gomez, K Michaelsson, MA Nalls, CM Nielson, L Oozageer, L Pascoe, L Paternoster, O Polasek, S Ripatti, MA Sarzynski, CS Shin, NS Narancic, D Spira, P Srikanth, E Steinhagen-Thiessen, YJ Sung, KMA Swart, L Taittonen, T Tanaka, E Tikkanen, Nathalie van der Velde, NM Schoor, N (Niek) Verweij, AF Wright, L Yu, JM Zmuda, N Eklund, T Forrester, N Grarup, AU Jackson, K Kristiansson, T Kuulasmaa, J Kuusisto, P Lichtner, JA Luan, A Mahajan, S Mannisto, CD Palmer, JS Ried, RA Scott, A Stancakova, PJ Wagner, Ayse Demirkan, A Doring, V Gudnason, DP Kiel, B Kuhnel, M Mangino, B McKnight, C Menni, JR O'Connell, Ben Oostra, AR Shuldiner, KJ Song, L Vandenput, Cornelia Duijn, P Vollenweider, CC White, M Boehnke, Y Boettcher, RS Cooper, NG Forouhi, C Gieger, H Grallert, A Hingorani, T Jorgensen, P Jousilahti, M Kivimaki, M Kumari, M Laakso, C Langenberg, A Linneberg, A Luke, CA McKenzie, A Palotie, O Pedersen, A Peters, K Strauch, BO Tayo, NJ Wareham, DA Bennett, L Bertram, J Blangero, M Bluher, C Bouchard, H Campbell, NH Cho, SR Cummings, SA Czerwinski, I Demuth, R Eckardt, JG Eriksson, L Ferrucci, OH Franco Duran, P Froguel, RT Gansevoort, T Hansen, TB Harris, N Hastie, M Heliovaara, Bert Hofman, JM Jordan, A Jula, M Kahonen, E Kajantie, PB Knekt, S Koskinen, P Kovacs, T Lehtimaki, L Lind, YM Liu, ES Orwoll, C Osmond, M Perola, L Perusse, OT Raitakari, T Rankinen, DC Rao, TK Rice, Fernando Rivadeneira, I Rudan, V Salomaa, TIA Sorensen, M Stumvoll, A Tonjes, B Towne, GJ Tranah, A Tremblay, André Uitterlinden, P van der Harst, E Vartiainen, JS Viikari, V Vitart, MC Vohl, H Volzke, M Walker, H Wallaschofski, S Wild, JF Wilson, L Yengo, DT Bishop, IB Borecki, JC Chambers, LA Cupples, Abbas Dehghan, P Deloukas, G Fatemifar, C Fox, TS Furey, L Franke, JL Han, DJ Hunter, J Karjalainen, F Karpe, RC Kaplan, JS Kooner, MI McCarthy, JM Murabito, AP Morris, JAN Bishop, KE North, C Ohlsson, KK Ong, I Prokopenko, JB Richards, EE Schadt, TD Spector, E Widen, CJ Willer, Jiaqi Yang, E Ingelsson, KL Mohlke, JN Hirschhorn, JA Pospisilik, M.C. Zillikens, C Lindgren, TO Kilpelainen, RJF Loos

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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.
Original languageUndefined/Unknown
JournalNature Communications
Volume7
DOIs
Publication statusPublished - 2016

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