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

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

doi:10.1038/nature14177

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.

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, C. Powell, S. Vedantam, M.L. Buchkovich, J. Yang, D.C. Croteau-Chonka, T. Esko, T. Fall, T. Ferreira, S. Gustafsson, Z. Kutalik, J. Luan, R. Mägi, J.C. Randall, T.W. Winkler, A.R. Wood, T. Workalemahu, J.D. Faul, J.A. Smith, J.H. Zhao, W. Zhao, J. Chen, R. Fehrmann, Å.K. Hedman, J. Karjalainen, E.M. Schmidt, D. Absher, N. Amin, D. Anderson, M. Beekman, J.L. Bolton, J.L. Bragg-Gresham, S. Buyske, A. Demirkan, G. Deng, 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-Gomez, 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.J. Sung, T. Tanaka, A. Teumer, S. Trompet, S.W. Van Der Laan, J. Van Setten, J.V. Van Vliet-Ostaptchouk, Z. Wang, L. Yengo, W. Zhang, A. Isaacs, E. Albrecht, J. Ärnlöv, G.M. Arscott, A.P. Attwood, 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.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, S.D. Gordon, M. Gorski, H. Grabe, H. Grallert, T.B. Grammer, J. Gräßler, H. Grönberg, C.J. Groves, G. Gusto, J. Haessler, P. Hall, T. Haller, G. Hallmans, C.A. Hartman, M. Hassinen, C. Hayward, N.L. Heard-Costa, Q. Helmer, C. Hengstenberg, O. Holmen, J. Hottenga, A.L. James, J.M. Jeff, Å. Johansson, J. Jolley, T. Juliusdottir, L. Kinnunen, W. Koenig, M. Koskenvuo, W. Kratzer, J. Laitinen, C. Lamina, K. Leander, N.R. Lee, P. Lichtner, L. Lind, J. Lindström, K.S. Lo, S. Lobbens, R. Lorbeer, Y. Lu, F. Mach, P.K.E. Magnusson, A. Mahajan, W.L. Mcardle, S. Mclachlan, C. Menni, S. Merger, E. Mihailov, L. Milani, A. Moayyeri, K.L. Monda, M.A. Morken, A. Mulas, G. Müller, M. Müller-Nurasyid, A.W. Musk, R. Nagaraja, M.M. Nöthen, I.M. Nolte, S. Pilz, N.W. Rayner, F. Renstrom, R. 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. Syvänen, S. Tan, B.O. Tayo, B. Thorand, G. Thorleifsson, J.P. Tyrer, H. Uh, L. Vandenput, F.C. Verhulst, S.H. Vermeulen, N. Verweij, J.M. Vonk, L.L. Waite, H.R. Warren, D. Waterworth, M.N. 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, J.R. Gådin, A.G. Gharavi, M.E. Goddard, R.E. Handsaker, J. Huang, F. Karpe, S. Kathiresan, S. Keildson, K. Kiryluk, M. Kubo, J. Lee, L. Liang, R.P. Lifton, B. Ma, S.A. Mccarroll, A.J. Mcknight, J.L. Min, M.F. Moffatt, G.W. Montgomery, J.M. Murabito, G. Nicholson, D.R. Nyholt, Y. Okada, J.R.B. Perry, R. Dorajoo, E. Reinmaa, R.M. Salem, N. Sandholm, R.A. Scott, L. Stolk, A. Takahashi, T. Tanaka, F.M. Va't Hooft, A.A.E. Vinkhuyzen, H. Westra, W. Zheng, K.T. Zondervan, A.C. Heath, D. Arveiler, S.J.L. Bakker, J. Beilby, R.N. Bergman, J. Blangero, P. Bovet, H. Campbell, M.J. Caulfield, G. Cesana, A. Chakravarti, D.I. Chasman, P.S. Chines, F.S. Collins, D.C. Crawford, L..A. Cupples, D. Cusi, J. Danesh, U. De Faire, H.M. Den Ruijter, A.F. Dominiczak, R. Erbel, J. Erdmann, J.G. Eriksson, M. 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. Gudnason, U. Gyllensten, A.S. Hall, T.B. Harris, A.T. Hattersley, A.A. Hicks, L.A. Hindorff, A.D. Hingorani, A. Hofman, G. Homuth, G..K. Hovingh, S.E. Humphries, S.C. Hunt, E. Hyppönen, T. Illig, K.B. Jacobs, M. Jarvelin, K. Jöckel, B. Johansen, P. Jousilahti, J..W. Jukema, A.M. Jula, J. Kaprio, J.J.P. Kastelein, S.M. Keinanen-Kiukaanniemi, L.A. Kiemeney, P. Knekt, J.S. Kooner, C. Kooperberg, P. Kovacs, A.T. Kraja, M. Kumari, J. Kuusisto, T.A. Lakka, C. Langenberg, L. Le Marchand, T. Lehtimäki, 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. Sever, A.R. Shuldiner, J. Sinisalo, R.P. Stolk, K. Strauch, A. Tönjes, D. Trégouët, A. Tremblay, E. Tremoli, J. Virtamo, M. Vohl, U. Völker, G. Waeber, G. Willemsen, J.C. Witteman, M..C. Zillikens, L.S. Adair, P. Amouyel, F.W. Asselbergs, T.L. Assimes, M. Bochud, B.O. Boehm, E. Boerwinkle, S.R. Bornstein, E.P. Bottinger, C. Bouchard, S. Cauchi, J.C. Chambers, S.J. Chanock, R.S. Cooper, P.I.W. De Bakker, G. Dedoussis, L. Ferrucci, P.W. Franks, P. Froguel, L.C. Groop, C.A. Haiman, A. Hamsten, J. 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. Metspalu, S. Moebus, P.B. Munroe, I. Njolstad, B.A. Oostra, C.N.A. Palmer, N.L. Pedersen, M. Perola, L. Pérusse, U. Peters, C. Power, T. Quertermous, R. Rauramaa, F. Rivadeneira, T.E. Saaristo, D. Saleheen, N. Sattar, E.E. Schadt, D. Schlessinger, P..E. Slagboom, H. Snieder, T.D. Spector, U. Thorsteinsdottir, M. Stumvoll, J. Tuomilehto, A.G. Uitterlinden, M. Uusitupa, P. Van Der Harst, M. Walker, H. Wallaschofski, N.J. Wareham, H. Watkins, D.R. Weir, H. 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. Stefansson, C.M. Van Duijn, G.R. Abecasis, L. Franke, T.M. Frayling, 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. - In: NATURE. - ISSN 0028-0836. - 518:7538(2015 Feb), pp. 197-206. [10.1038/nature14177]

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;C. Powell;S. Vedantam;M. L. Buchkovich;J. Yang;D. C. Croteau Chonka;T. Esko;T. Fall;T. Ferreira;S. Gustafsson;Z. Kutalik;J. Luan;R. Mägi;J. C. Randall;T. W. Winkler;A. R. Wood;T. Workalemahu;J. D. Faul;J. A. Smith;J. H. Zhao;W. Zhao;J. Chen;R. Fehrmann;Å. K. Hedman;J. Karjalainen;E. M. Schmidt;D. Absher;N. Amin;D. Anderson;M. Beekman;J. L. Bolton;J. L. Bragg Gresham;S. Buyske;A. Demirkan;G. Deng;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 Gomez;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. J. Sung;T. Tanaka;A. Teumer;S. Trompet;S. W. Van Der Laan;J. Van Setten;J. V. Van Vliet Ostaptchouk;Z. Wang;L. Yengo;W. Zhang;A. Isaacs;E. Albrecht;J. Ärnlöv;G. M. Arscott;A. P. Attwood;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. 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;S. D. Gordon;M. Gorski;H. Grabe;H. Grallert;T. B. Grammer;J. Gräßler;H. Grönberg;C. J. Groves;G. Gusto;J. Haessler;P. Hall;T. Haller;G. Hallmans;C. A. Hartman;M. Hassinen;C. Hayward;N. L. Heard Costa;Q. Helmer;C. Hengstenberg;O. Holmen;J. Hottenga;A. L. James;J. M. Jeff;Å. Johansson;J. Jolley;T. Juliusdottir;L. Kinnunen;W. Koenig;M. Koskenvuo;W. Kratzer;J. Laitinen;C. Lamina;K. Leander;N. R. Lee;P. Lichtner;L. Lind;J. Lindström;K. S. Lo;S. Lobbens;R. Lorbeer;Y. Lu;F. Mach;P. K. E. Magnusson;A. Mahajan;W. L. Mcardle;S. Mclachlan;C. Menni;S. Merger;E. Mihailov;L. Milani;A. Moayyeri;K. L. Monda;M. A. Morken;A. Mulas;G. Müller;M. Müller Nurasyid;A. W. Musk;R. Nagaraja;M. M. Nöthen;I. M. Nolte;S. Pilz;N. W. Rayner;F. Renstrom;R. 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. Syvänen;S. Tan;B. O. Tayo;B. Thorand;G. Thorleifsson;J. P. Tyrer;H. Uh;L. Vandenput;F. C. Verhulst;S. H. Vermeulen;N. Verweij;J. M. Vonk;L. L. Waite;H. R. Warren;D. Waterworth;M. N. 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;J. R. Gådin;A. G. Gharavi;M. E. Goddard;R. E. Handsaker;J. Huang;F. Karpe;S. Kathiresan;S. Keildson;K. Kiryluk;M. Kubo;J. Lee;L. Liang;R. P. Lifton;B. Ma;S. A. Mccarroll;A. J. Mcknight;J. L. Min;M. F. Moffatt;G. W. Montgomery;J. M. Murabito;G. Nicholson;D. R. Nyholt;Y. Okada;J. R. B. Perry;R. Dorajoo;E. Reinmaa;R. M. Salem;N. Sandholm;R. A. Scott;L. Stolk;A. Takahashi;T. Tanaka;F. M. Va't Hooft;A. A. E. Vinkhuyzen;H. Westra;W. Zheng;K. T. Zondervan;A. C. Heath;D. Arveiler;S. J. L. Bakker;J. Beilby;R. N. Bergman;J. Blangero;P. Bovet;H. Campbell;M. J. Caulfield;G. Cesana;A. Chakravarti;D. I. Chasman;P. S. Chines;F. S. Collins;D. C. Crawford;L. . A. Cupples;D. Cusi;J. Danesh;U. De Faire;H. M. Den Ruijter;A. F. Dominiczak;R. Erbel;J. Erdmann;J. G. Eriksson;M. 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. Gudnason;U. Gyllensten;A. S. Hall;T. B. Harris;A. T. Hattersley;A. A. Hicks;L. A. Hindorff;A. D. Hingorani;A. Hofman;G. Homuth;G. . K. Hovingh;S. E. Humphries;S. C. Hunt;E. Hyppönen;T. Illig;K. B. Jacobs;M. Jarvelin;K. Jöckel;B. Johansen;P. Jousilahti;J. . W. Jukema;A. M. Jula;J. Kaprio;J. J. P. Kastelein;S. M. Keinanen Kiukaanniemi;L. A. Kiemeney;P. Knekt;J. S. Kooner;C. Kooperberg;P. Kovacs;A. T. Kraja;M. Kumari;J. Kuusisto;T. A. Lakka;C. Langenberg;L. Le Marchand;T. Lehtimäki;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. Sever;A. R. Shuldiner;J. Sinisalo;R. P. Stolk;K. Strauch;A. Tönjes;D. Trégouët;A. Tremblay;E. Tremoli;J. Virtamo;M. Vohl;U. Völker;G. Waeber;G. Willemsen;J. C. Witteman;M. . C. Zillikens;L. S. Adair;P. Amouyel;F. W. Asselbergs;T. L. Assimes;M. Bochud;B. O. Boehm;E. Boerwinkle;S. R. Bornstein;E. P. Bottinger;C. Bouchard;S. Cauchi;J. C. Chambers;S. J. Chanock;R. S. Cooper;P. I. W. De Bakker;G. Dedoussis;L. Ferrucci;P. W. Franks;P. Froguel;L. C. Groop;C. A. Haiman;A. Hamsten;J. 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. Metspalu;S. Moebus;P. B. Munroe;I. Njolstad;B. A. Oostra;C. N. A. Palmer;N. L. Pedersen;M. Perola;L. Pérusse;U. Peters;C. Power;T. Quertermous;R. Rauramaa;F. Rivadeneira;T. E. Saaristo;D. Saleheen;N. Sattar;E. E. Schadt;D. Schlessinger;P. . E. Slagboom;H. Snieder;T. D. Spector;U. Thorsteinsdottir;M. Stumvoll;J. Tuomilehto;A. G. Uitterlinden;M. Uusitupa;P. Van Der Harst;M. Walker;H. Wallaschofski;N. J. Wareham;H. Watkins;D. R. Weir;H. 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. Stefansson;C. M. Van Duijn;G. R. Abecasis;L. Franke;T. M. Frayling;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

2015

Abstract

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.

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Scheda completa

Scheda completa (DC)

	Parole chiave
	
			Adipogenesis; Adiposity; Age Factors; Continental Population Groups; Energy Metabolism; Europe; Female; Genetic Predisposition to Disease; Glutamic Acid; Humans; Insulin; Male; Obesity; Polymorphism, Single Nucleotide; Quantitative Trait Loci; Synapses; Body Mass Index; Genome-Wide Association Study; Multidisciplinary
		
	Settori scientifico-disciplinari dell'articolo
	
			Settore BIO/18 - Genetica
		
	Data di pubblicazione
	
			feb-2015
		
	Rivista in ANCE
	
			NATURE
		
	DOI
	
			https://dx.doi.org/10.1038/nature14177
		
	Tipologia
	
			Article (author)
		
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			01 - Articolo su periodico

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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2434/282824

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