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Genetic studies of body mass index yield new insights for obesity biology.
Locke, Adam E. 1; Kahali, Bratati 2; Berndt, Sonja I. 3; Justice, Anne E. 4; Pers, Tune H. 5,6,7,8; Day, Felix R. 9; Powell, Corey 2; Vedantam, Sailaja 5,6; Buchkovich, Martin L. 10; Yang, Jian 11,12; Croteau-Chonka, Damien C. 10,13; Esko, Tonu 5,6,7,14; Fall, Tove 15,16,17; Ferreira, Teresa 18; Gustafsson, Stefan 16,17; Kutalik, Zoltan 19,20,21; Luan, Jian'an 9; Magi, Reedik 14,18; Randall, Joshua C. 18,22; Winkler, Thomas W. 23; Wood, Andrew R. 24; Workalemahu, Tsegaselassie 25; Faul, Jessica D. 26; Smith, Jennifer A. 27; Hua Zhao, Jing 9; Zhao, Wei 27; Chen, Jin 28; Fehrmann, Rudolf 29; Hedman, Asa K. 16,17,18; Karjalainen, Juha 29; Schmidt, Ellen M. 30; Absher, Devin 31; Amin, Najaf 32; Anderson, Denise 33; Beekman, Marian 34,35; Bolton, Jennifer L. 36; Bragg-Gresham, Jennifer L. 1,37; Buyske, Steven 38,39; Demirkan, Ayse 32,40; Deng, Guohong 41,42,43; Ehret, Georg B. 44,45; Feenstra, Bjarke 46; Feitosa, Mary F. 47; Fischer, Krista 14; Goel, Anuj 18,48; Gong, Jian 49; Jackson, Anne U. 1; Kanoni, Stavroula 50; Kleber, Marcus E. 51,52; Kristiansson, Kati 53; Lim, Unhee 54; Lotay, Vaneet 55; Mangino, Massimo 56; Mateo Leach, Irene 57; Medina-Gomez, Carolina 58,59,60; Medland, Sarah E. 61; Nalls, Michael A. 62; Palmer, Cameron D. 5,6; Pasko, Dorota 24; Pechlivanis, Sonali 63; Peters, Marjolein J. 58,60; Prokopenko, Inga 18,64,65; Shungin, Dmitry 66,67,68; Stancakova, Alena 69; Strawbridge, Rona J. 70; Ju Sung, Yun 71; Tanaka, Toshiko 72; Teumer, Alexander 73; Trompet, Stella 74,75; van der Laan, Sander W. 76; van Setten, Jessica 77; Van Vliet-Ostaptchouk, Jana V. 78; Wang, Zhaoming 3,79; Yengo, Loic 80,81,82; Zhang, Weihua 41,83; Isaacs, Aaron 32,84; Albrecht, Eva 85; Arnlov, Johan 16,17,86; Arscott, Gillian M. 87; Attwood, Antony P. 88,89; Bandinelli, Stefania 90; Barrett, Amy 64; Bas, Isabelita N. 91; Bellis, Claire 92,93; Bennett, Amanda J. 64; Berne, Christian 94; Blagieva, Roza 95; Bluher, Matthias 96,97; Bohringer, Stefan 34,98; Bonnycastle, Lori L. 99; Bottcher, Yvonne 96; Boyd, Heather A. 46; Bruinenberg, Marcel 100; Caspersen, Ida H. 101; Ida Chen, Yii-Der 102,103; Clarke, Robert 104; Warwick Daw, E. 47; de Craen, Anton J. 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L. 220; Beilby, John 87,221; Bergman, Richard N. 222; Blangero, John 92; Bovet, Pascal 223,224; Campbell, Harry 36; Caulfield, Mark J. 181; Cesana, Giancarlo 225; Chakravarti, Aravinda 44; Chasman, Daniel I. 163,226; Chines, Peter S. 99; Collins, Francis S. 99; Crawford, Dana C. 227,228; Adrienne Cupples, L. 127,229; Cusi, Daniele 230,231; Danesh, John 232; de Faire, Ulf 111; den Ruijter, Hester M. 76,233; Dominiczak, Anna F. 234; Erbel, Raimund 235; Erdmann, Jeanette 183,184; Eriksson, Johan G. 53,236,237; Farrall, Martin 18,48; Felix, Stephan B. 238,239; Ferrannini, Ele 240,241; Ferrieres, Jean 242; Ford, Ian 243; Forouhi, Nita G. 9; Forrester, Terrence 244; Franco, Oscar H. 58,59; Gansevoort, Ron T. 220; Gejman, Pablo V. 245; Gieger, Christian 85; Gottesman, Omri 55; Gudnason, Vilmundur 167,168; Gyllensten, Ulf 136; Hall, Alistair S. 246; Harris, Tamara B. 109; Hattersley, Andrew T. 247; Hicks, Andrew A. 248; Hindorff, Lucia A. 249; Hingorani, Aroon D. 250; Hofman, Albert 58,59; Homuth, Georg 73; Kees Hovingh, G. 251; Humphries, Steve E. 252; Hunt, Steven C. 253; Hypponen, Elina 254,255,256,257; Illig, Thomas 119,258; Jacobs, Kevin B. 3,79; Jarvelin, Marjo-Riitta 83,259,260,261,263,263; Jockel, Karl-Heinz 63; Johansen, Berit 101; Jousilahti, Pekka 53; Wouter Jukema, J. 74,264,265; Jula, Antti M. 53; Kaprio, Jaakko 53,107,137; Kastelein, John J. P. 251; Keinanen-Kiukaanniemi, Sirkka M. 263,266; Kiemeney, Lambertus A. 179,267; Knekt, Paul 53; Kooner, Jaspal S. 41,173,268; Kooperberg, Charles 49; Kovacs, Peter 96,97; Kraja, Aldi T. 47; Kumari, Meena 269,270; Kuusisto, Johanna 271; Lakka, Timo A. 125,272,273; Langenberg, Claudia 9,269; Le Marchand, Loic 54; Lehtimaki, Terho 274; Lyssenko, Valeriya 275,276; Mannisto, Satu 53; Marette, Andre 277,278; Matise, Tara C. 39; McKenzie, Colin A. 244; McKnight, Barbara 279; Moll, Frans L. 280; Morris, Andrew D. 106; Morris, Andrew P. 14,18,281; Murray, Jeffrey C. 282; Nelis, Mari 14; Ohlsson, Claes 177; Oldehinkel, Albertine J. 124; Ong, Ken K. 9,186; Madden, Pamela A. F. 218; Pasterkamp, Gerard 76; Peden, John F. 283; Peters, Annette 119,130,175; Postma, Dirkje S. 284; Pramstaller, Peter P. 248,285; Price, Jackie F. 36; Qi, Lu 13,25; Raitakari, Olli T. 286,287; Rankinen, Tuomo 288; Rao, D. C. 47,71,218; Rice, Treva K. 71,218; Ridker, Paul M. 163,226; Rioux, John D. 143,289; Ritchie, Marylyn D. 290; Rudan, Igor 36,291; Salomaa, Veikko 53; Samani, Nilesh J. 114,115; Saramies, Jouko 292; Sarzynski, Mark A. 288; Schunkert, Heribert 130,131; Schwarz, Peter E. H. 121,293; Sever, Peter 294; Shuldiner, Alan R. 295,296,297; Sinisalo, Juha 298; Stolk, Ronald P. 169; Strauch, Konstantin 85,153; Tonjes, Anke 96,97; Tregouet, David-Alexandre 299,300,301; Tremblay, Angelo 302; Tremoli, Elena 303; Virtamo, Jarmo 53; Vohl, Marie-Claude 278,304; Volker, Uwe 73,239; Waeber, Gerard 305; Willemsen, Gonneke 133; Witteman, Jacqueline C. 59; Carola Zillikens, M. 58,60; Adair, Linda S. 306; Amouyel, Philippe 307; Asselbergs, Folkert W. 250,264,308; Assimes, Themistocles L. 309; Bochud, Murielle 223,224; Boehm, Bernhard O. 310,311; Boerwinkle, Eric 312; Bornstein, Stefan R. 121; Bottinger, Erwin P. 55; Bouchard, Claude 288; Cauchi, Stephane 80,81,82; Chambers, John C. 41,83,268; Chanock, Stephen J. 3; Cooper, Richard S. 174; de Bakker, Paul I. W. 77,313,314; Dedoussis, George 105; Ferrucci, Luigi 72; Franks, Paul W. 25,66,67; Froguel, Philippe 65,80,81,82; Groop, Leif C. 107,276; Haiman, Christopher A. 165; Hamsten, Anders 70; Hui, Jennie 87,221,315; Hunter, David J. 13,25,194; Hveem, Kristian 132; Kaplan, Robert C. 316; Kivimaki, Mika 269; Kuh, Diana 186; Laakso, Markku 271; Liu, Yongmei 317; Martin, Nicholas G. 61; Marz, Winfried 51,164,318; Melbye, Mads 309,319; Metspalu, Andres 14,147; Moebus, Susanne 63; Munroe, Patricia B. 181; Njolstad, Inger 185; Oostra, Ben A. 32,84,320; Palmer, Colin N. A. 106; Pedersen, Nancy L. 15; Perola, Markus 14,53,107; Perusse, Louis 278,302; Peters, Ulrike 49; Power, Chris 257; Quertermous, Thomas 309; Rauramaa, Rainer 125,273; Rivadeneira, Fernando 58,59,60; Saaristo, Timo E. 321,322; Saleheen, Danish 232,323,324; Sattar, Naveed 325; Schadt, Eric E. 326; Schlessinger, David 155; Eline Slagboom, P. 34,35; Snieder, Harold 169; Spector, Tim D. 56; Thorsteinsdottir, Unnur 171,327; Stumvoll, Michael 96,97; Tuomilehto, Jaakko 53,328,329,330; Uitterlinden, Andre G. 58,59,60; Uusitupa, Matti 331,332; van der Harst, Pim 29,57,264; Walker, Mark 333; Wallaschofski, Henri 239,334; Wareham, Nicholas J. 9; Watkins, Hugh 18,48; Weir, David R. 26; Wichmann, H-Erich 335,336,337; Wilson, James F. 36; Zanen, Pieter 338; Borecki, Ingrid B. 47; Deloukas, Panos 22,50,339; Fox, Caroline S. 127; Heid, Iris M. 23,85; O'Connell, Jeffrey R. 295,296; Strachan, David P. 340; Stefansson, Kari 171,327; van Duijn, Cornelia M. 32,58,59,84; Abecasis, Goncalo R. 1; Franke, Lude 29; Frayling, Timothy M. 24; McCarthy, Mark I. 18,64,341; Visscher, Peter M. 11,12; Scherag, Andre 63,342; Willer, Cristen J. 28,30,343; Boehnke, Michael 1; Mohlke, Karen L. 10; Lindgren, Cecilia M. 6,18; Beckmann, Jacques S. 20,21,344; Barroso, Ines 22,345,346; North, Kari E. 4,347; Ingelsson, Erik 16,17,18; Hirschhorn, Joel N. 5,6,7,+; Loos, Ruth J. F. 9,55,145,348,+; Speliotes, Elizabeth K. 2,*
[Article] Nature. 518(7538):197-206, February 12, 2015.

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: 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 x 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.