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.
New loci for body fat percentage reveal link between adiposity and cardiometabolic disease risk / Y. Lu, F. Day, S. Gustafsson, M. Buchkovich, J. Na, V. Bataille, D. Cousminer, Z. Dastani, A. Drong, T. Esko, D. Evans, M. Falchi, M. Feitosa, T. Ferreira, A. Hedman, R. Haring, P. Hysi, M. Iles, A. Justice, S. Kanoni, V. Lagou, R. Li, X. Li, A. Locke, C. Lu, R. Magi, J. Perry, T. Pers, Q. Qi, M. Sanna, E. Schmidt, W. Scott, D. Shungin, A. Teumer, A. Vinkhuyzen, R. Walker, H. Westra, M. Zhang, W. Zhang, J. Zhao, Z. Zhu, U. Afzal, T. Ahluwalia, S. Bakker, C. Bellis, A. Bonnefond, K. Borodulin, A. Buchman, T. Cederholm, A. Choh, H. Choi, J. Curran, L. de Groot, P. De Jager, R. Dhonukshe-Rutten, A. Enneman, E. Eury, D. Evans, T. Forsen, N. Friedrich, F. Fumeron, M. Garcia, S. Gartner, B. Han, A. Havulinna, C. Hayward, D. Hernandez, H. Hillege, T. Ittermann, J. Kent, I. Kolcic, T. Laatikainen, J. Lahti, I. Leach, C. Lee, J. Lee, T. Liu, Y. Liu, S. Lobbens, M. Loh, L. Lyytikainen, C. Medina-Gomez, K. Michaelsson, M. Nalls, C. Nielson, L. Oozageer, L. Pascoe, L. Paternoster, O. Polasek, S. Ripatti, M. Sarzynski, C. Shin, N. Narancic, D. Spira, P. Srikanth, E. Steinhagen-Thiessen, Y. Sung, K. Swart, L. Taittonen, T. Tanaka, E. Tikkanen, N. van der Velde, N. van Schoor, N. Verweij, A. Wright, L. Yu, J. Zmuda, N. Eklund, T. Forrester, N. Grarup, A. Jackson, K. Kristiansson, T. Kuulasmaa, J. Kuusisto, P. Lichtner, J. Luan, A. Mahajan, S. Mannisto, C. Palmer, J. Ried, R. Scott, A. Stancakova, P. Wagner, A. Demirkan, A. Doring, V. Gudnason, D. Kiel, B. Kuhnel, M. Mangino, B. Mcknight, C. Menni, J. O'Connell, B. Oostra, A. Shuldiner, K. Song, L. Vandenput, C. van Duijn, P. Vollenweider, C. White, M. Boehnke, Y. Boettcher, R. Cooper, N. Forouhi, C. Gieger, H. Grallert, A. Hingorani, T. Jorgensen, P. Jousilahti, M. Kivimaki, M. Kumari, M. Laakso, C. Langenberg, A. Linneberg, A. Luke, C. Mckenzie, A. Palotie, O. Pedersen, A. Peters, K. Strauch, B. Tayo, N. Wareham, D. Bennett, L. Bertram, J. Blangero, M. Bluher, C. Bouchard, H. Campbell, N. Cho, S. Cummings, S. Czerwinski, I. Demuth, R. Eckardt, J. Eriksson, L. Ferrucci, O. Franco, P. Froguel, R. Gansevoort, T. Hansen, T. Harris, N. Hastie, M. Heliovaara, A. Hofman, J. Jordan, A. Jula, M. Kahonen, E. Kajantie, P. Knekt, S. Koskinen, P. Kovacs, T. Lehtimaki, L. Lind, Y. Liu, E. Orwoll, C. Osmond, M. Perola, L. Perusse, O. Raitakari, T. Rankinen, D. Rao, T. Rice, F. Rivadeneira, I. Rudan, V. Salomaa, T. Sorensen, M. Stumvoll, A. Tonjes, B. Towne, G. Tranah, A. Tremblay, A. Uitterlinden, P. van der Harst, E. Vartiainen, J. Viikari, V. Vitart, M. Vohl, H. Volzke, M. Walker, H. Wallaschofski, S. Wild, J. Wilson, L. Yengo, D. Bishop, I. Borecki, J. Chambers, L. Cupples, A. Dehghan, P. Deloukas, G. Fatemifar, C. Fox, T. Furey, L. Franke, J. Han, D. Hunter, J. Karjalainen, F. Karpe, R. Kaplan, J. Kooner, M. Mccarthy, J. Murabito, A. Morris, J. Bishop, K. North, C. Ohlsson, K. Ong, I. Prokopenko, J. Richards, E. Schadt, T. Spector, E. Widen, C. Willer, J. Yang, E. Ingelsson, K. Mohlke, J. Hirschhorn, J. Pospisilik, M. Zillikens, C. Lindgren, T. Kilpelainen, R. Loos. - In: NATURE COMMUNICATIONS. - ISSN 2041-1723. - 7:(2016), pp. 10495.1-10495.15. [10.1038/ncomms10495]
New loci for body fat percentage reveal link between adiposity and cardiometabolic disease risk
C. Menni;
2016
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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