Genetic studies of body mass index yield new insights for obesity biology

A.E. Locke, B. Kahali, S.I. Berndt, A.E. Justice, T.H. Pers, F.R. Day, S. Vedantam, M.L. Buchkovich, J. Yang, D.C. Croteau- Chonka, T. Esko, T. Fall, T.C. Ferreira, S. Gustafsson, Z. Kutalik, R. Mägi, J.C. Randall, T.W. Winkler, A.R. Wood, T. WorkalemahuJ.D. Faul, J.A. Smith, J. Zhao, W. Zhao, J. Chen, R.S.N. Fehrmann, A.K. Hedman, J.M. Karjalainen, E.M. Schmidt, D.M. Absher, N. Amin, Denise Anderson, M. Beekman, J.L. Bolton, S.G. Buyske, A. Demirkan, G.B. Ehret, B. Feenstra, M.F. Feitosa, K. Fischer, A. Goel, J. Gong, A.U. Jackson, S. Kanoni, M.E. Kleber, K. Kristiansson, U. Lim, V. Lotay, M. Mangino, I.M. Leach, C. Medina-Gómez, S.E. Medland, M.A. Nalls, C.D. Palmer, D. Pasko, S. Pechlivanis, M.J. Peters, I. Prokopenko, D. Shungin, A. Stančáková, R.J. Strawbridge, Y. Sung, T. Tanaka, A. Teumer, S. Trompet, S.W. Van Der Laan, J.A. Van Setten, J.V. Van Vliet-Ostaptchouk, Z. Wang, L. Yengo, W. Zhang, A. Isaacs, E. Albrecht, J. Ärnlöv, G. Arscott, A.P. Attwood, S.S. Bandinelli, A. Barrett, I.N. Bas, C. Bellis, A.J. Bennett, C. Berne, R. Blagieva, M. Blüher, S. Böhringer, L.L. Bonnycastle, Y. Böttcher, H.A. Boyd, M. Bruinenberg, I.H. Caspersen, Y.D.I. Chen, R. Clarke, E.W. Daw, A.J.M. De Craen, G. Delgado, M. Dimitriou, A.S.F. Doney, N. Eklund, K. Estrada, E. Eury, L. Folkersen, R.M. Fraser, M.E. Garcia, F. Geller, V. Giedraitis, B. Gigante, A.S. Go, A. Golay, A.H. Goodall, M.M. Gorski, H.J. Grabe, H. Grallert, T.B. Grammer, J. Gräßler, H. Gron̈berg, C.J. Groves, G. Gusto, J. Haessler, P. Hall, T. Haller, C.A. Hartman, M. Hassinen, C. Hayward, N.L. Heard-Costa, Q. Helmer, C. Hengstenberg, O.L. Holmen, J.J. Hottenga, Alan James, J.M. Jeff, A.M. Johansson, J.D.M. Jolley, T. Juliusdottir, L. Kinnunen, W. Koenig, W. Kratzer, J.H. Laitinen, C. Lamina, K. Leander, N. Lee, P.K. Lichtner, L. Lind, J. Lindström, K. Lo, R. Lorbeer, Y. Lu, F.R.A. Mach, P.K.E. Magnusson, A. Mahajan, W.L. Mcardle, S. Mclachlan, C. Menni, S.R. Merger, E. Mihailov, L. Milani, A. Moayyeri, K.L. Monda, M.A. Morken, A. Mulas, G.F. Müller, M. Müller-Nurasyid, A.W.B.M. Musk, R. Nagaraja, M.M. Nöthen, I.M. Nolte, S. Pilz, N.W. Rayner, F. Renström, R.L. Rettig, J.S. Ried, S. Ripke, N.R. Robertson, L.M. Rose, S. Sanna, H. Scharnagl, S. Scholtens, F.R. Schumacher, W.R. Scott, T. Seufferlein, J. Shi, A.V. Smith, J. Smolonska, A.V. Stanton, V. Steinthorsdottir, K. Stirrups, H.M. Stringham, J. Sundström, M.A. Swertz, A.J. Swift, A.C. Syvänen, S. Tan, B. Tayo, B. Thorand, G. Thorleifsson, J.P. Tyrer, L. Vandenput, F.C.C. Verhulst, S.H.H.M. Vermeulen, N. Verweij, J.M. Vonk, L.L. Waite, D.M. Waterworth, M. Weedon, L.R. Wilkens, C. Willenborg, T. Wilsgaard, M.K. Wojczynski, A. Wong, A.F. Wright, Q. Zhang, E.P. Brennan, M. Choi, Z. Dastani, A.W. Drong, P. Eriksson, A. Franco-Cereceda, A.G. Gharavi, M.E. Goddard, R.E. Handsaker, J. Huang, F. Karpe, S. Kathiresan, S. Keildson, K. Kiryluk, L. Liang, R.P. Lifton, B. Ma, S.A. Mccarroll, A.J. Mcknight, M.F. Moffatt, G.W. Montgomery, J.M. Murabito, G.D. Nicholson, D.R. Nyholt, J.R.B. Perry, R.S.O. Dorajoo, E. Reinmaa, R.M. Salem, N. Sandholm, R.A. Scott, L. Stolk, A.A.E. Vinkhuyzen, H.J. Westra, W. Zheng, K.T. Zondervan, A.C. Heath, D. Arveiler, S.J.L. Bakker, John Beilby, R.N. Bergman, J.C. Blangero, P. Bovet, H. Campbell, M. Caulfield, G.C. Cesana, D.I. Chasman, P.S. Chines, F.S. Collins, D.C. Crawford, L.A. Cupples, D.M. Cusi, J. Danesh, U.H. Dé Fairé, H.M. Den Ruijter, A.F.D. Dominiczak, R.M. Erbel, J. Erdmann, J.G. Eriksson, M.J. Farrall, S.B. Felix, E. Ferrannini, J. Ferrières, I. Ford, N.G. Forouhi, T. Forrester, O.H. Franco, R.T. Gansevoort, P.V. Gejman, C. Gieger, O. Gottesman, V.G. Gudnason, U.B. Gyllensten, A.S. Hall, T.B. Harris, A. Hattersley, A.A. Hicks, L.A. Hindorff, A.D. Hingorani, A. Hofman, G. Homuth, G.K. Hovingh, S.E. Humphries, E. Hypponen, T. Illig, M. Järvelin, K.H. Jöckel, B. Johansen, P.J. Jousilahti, J.W. Jukema, A.M. Jula, J.I. Kaprio, J.J.P. Kastelein, S.M. Keinänen-Kiukaanniemi, L.A.L.M.B. Kiemeney, P. Knekt, J.S. Kooner, C.L. Kooperberg, P. Kovács, A.T. Kraja, M. Kumari, J. Kuusisto, T.A. Lakka, C. Langenberg, L. Le Marchand, V. Lyssenko, S. Männistö, A. Marette, T.C. Matise, C.A. Mckenzie, B. Mcknight, F.L. Moll, A.D. Morris, A.P. Morris, J.C. Murray, M. Nelis, C. Ohlsson, A.J. Oldehinkel, K.K. Ong, P.A.F. Madden, G. Pasterkamp, J.F. Peden, A. Peters, D.S. Postma, P.P. Pramstaller, J.F. Price, L. Qi, O.T. Raitakari, T. Rankinen, D.C. Rao, T.K. Rice, P.M. Ridker, J.D. Rioux, M.D. Ritchie, I. Rudan, V. Salomaa, N.J. Samani, J. Saramies, M.A. Sarzynski, H. Schunkert, P.E.H. Schwarz, P.S. Sever, A.R. Shuldiner, J.P. Sinisalo, R.P. Stolk, K.K. Strauch, A. Tönjes, D.A. Trégouët, A. Tremblay, E. Tremoli, J.R.K. Virtamo, M.C. Vohl, U.U. Völker, G. Waeber, G.A.H.M. Willemsen, J.C.M. Witteman, M.C.C. Zillikens, L.S. Adair, P. Amouyel, F.W. Asselbergs, T.L. Assîmes, M. Bochud, B.O. Boehm, E.E. Boerwinkle, S.R. Bornstein, E.P. Bottinger, C. Bouchard, S.S. Cauchi, J.C. Chambers, S.J. Chanock, R.S. Cooper, P.I.W. De Bakker, G.V.Z. Dedoussis, L. Ferrucci, P.W. Franks, P.H. Froguel, L.C. Groop, C.A. Haiman, A. Hamsten, Jennie Hui, D.J. Hunter, K. Hveem, R.C. Kaplan, M. Kivimaki, D. Kuh, M. Laakso, Y. Liu, N.G. Martin, W. März, M. Melbye, A.K. Metspalu, S. Moebus, P.B. Munroe, I. Njølstad, B.A. Oostra, C.N.A. Palmer, N.L. Pedersen, M. Perola, L. Pérusse, U. Peters, C. Power, T. Quertermous, R. Rauramaa, F.F. Rivadeneira, T.E. Saaristo, D. Saleheen, N.A. Sattar, E.E. Schadt, D. Schlessinger, P.E. Slagboom, H. Snieder, T.D. Spector, U. Thorsteinsdóttir, M.W. Stumvoll, J.O.I. Tuomilehto, A.G. Uitterlinden, M. Uusitupa, P. Van Der Harst, M. A. Walker, H. Wallaschofski, N.J. Wareham, H. Watkins, D.R. Weir, H.E. Wichmann, J.F. Wilson, P. Zanen, I.B. Borecki, P. Deloukas, C.S. Fox, I.M. Heid, J.R. O'Connell, D.P. Strachan, K. Stefánsson, C.M. Van Duijn, G.R. Abeçasis, L. Franke, M.I. Mccarthy, P.M. Visscher, A. Scherag, C.J. Willer, M. Boehnke, K.L. Mohlke, C.M. Lindgren, J.S. Beckmann, I. Barroso, K.E. North, E. Ingelsson, J.N. Hirschhorn, R.J.F. Loos, E.K. Speliotes

Research output: Contribution to journalArticle

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Abstract

© 2015 Macmillan Publishers Limited. All rights reserved. Obesity is heritable and predisposes to many diseases. To understand the genetic basis of obesity better, here we conduct a genome-wide association study and Metabochip meta-analysis of body mass index (BMI), a measure commonly used to define obesity and assess adiposity, in up to 339,224 individuals. This analysis identifies 97 BMI-associated loci (P <5 × 10-8), 56 of which are novel. Five loci demonstrate clear evidence of several independent association signals, and many loci have significant effects on other metabolic phenotypes. The 97 loci account for ∼2.7% of BMI variation, and genome-wide estimates suggest that common variation accounts for >20% of BMI variation. Pathway analyses provide strong support for a role of the central nervous system in obesity susceptibility and implicate new genes and pathways, including those related to synaptic function, glutamate signalling, insulin secretion/action, energy metabolism, lipid biology and adipogenesis.
Original languageEnglish
Pages (from-to)197-206
JournalNature
Volume518
Issue number7538
DOIs
Publication statusPublished - 2015

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    Locke, A. E., Kahali, B., Berndt, S. I., Justice, A. E., Pers, T. H., Day, F. R., ... Speliotes, E. K. (2015). Genetic studies of body mass index yield new insights for obesity biology. Nature, 518(7538), 197-206. https://doi.org/10.1038/nature14177