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

Authors:
Adam E Locke, Bratati Kahali, Sonja I Berndt, Anne E Justice, Tune H Pers, Felix R Day, Corey Powell, Sailaja Vedantam, Martin L Buchkovich, Jian Yang, Damien C Croteau-Chonka, Tonu Esko, Tove Fall, Teresa Ferreira, Stefan Gustafsson, Zoltán Kutalik, Jian'an Luan, Reedik Mägi, Joshua C Randall, Thomas W Winkler, Andrew R Wood, Tsegaselassie Workalemahu, Jessica D Faul, Jennifer A Smith, Jing Hua Zhao, Wei Zhao, Jin Chen, Rudolf Fehrmann, Åsa K Hedman, Juha Karjalainen, Ellen M Schmidt, Devin Absher, Najaf Amin, Denise Anderson, Marian Beekman, Jennifer L Bolton, Jennifer L Bragg-Gresham, Steven Buyske, Ayse Demirkan, Guohong Deng, Georg B Ehret, Bjarke Feenstra, Mary F Feitosa, Krista Fischer, Anuj Goel, Jian Gong, Anne U Jackson, Stavroula Kanoni, Marcus E Kleber, Kati Kristiansson, Unhee Lim, Vaneet Lotay, Massimo Mangino, Irene Mateo Leach, Carolina Medina-Gomez, Sarah E Medland, Michael A Nalls, Cameron D Palmer, Dorota Pasko, Sonali Pechlivanis, Marjolein J Peters, Inga Prokopenko, Dmitry Shungin, Alena Stančáková, Rona J Strawbridge, Yun Ju Sung, Toshiko Tanaka, Alexander Teumer, Stella Trompet, Sander W van der Laan, Jessica van Setten, Jana V Van Vliet-Ostaptchouk, Zhaoming Wang, Loïc Yengo, Weihua Zhang, Aaron Isaacs, Eva Albrecht, Johan Ärnlöv, Gillian M Arscott, Antony P Attwood, Stefania Bandinelli, Amy Barrett, Isabelita N Bas, Claire Bellis, Amanda J Bennett, Christian Berne, Roza Blagieva, Matthias Blüher, Stefan Böhringer, Lori L Bonnycastle, Yvonne Böttcher, Heather A Boyd, Marcel Bruinenberg, Ida H Caspersen, Yii-Der Ida Chen, Robert Clarke, E Warwick Daw, Anton J M de Craen, Graciela Delgado, Maria Dimitriou, Alex S F Doney, Niina Eklund, Karol Estrada, Elodie Eury, Lasse Folkersen, Ross M Fraser, Melissa E Garcia, Frank Geller, Vilmantas Giedraitis, Bruna Gigante, Alan S Go, Alain Golay, Alison H Goodall, Scott D Gordon, Mathias Gorski, Hans-Jörgen Grabe, Harald Grallert, Tanja B Grammer, Jürgen Gräßler, Henrik Grönberg, Christopher J Groves, Gaëlle Gusto, Jeffrey Haessler, Per Hall, Toomas Haller, Goran Hallmans, Catharina A Hartman, Maija Hassinen, Caroline Hayward, Nancy L Heard-Costa, Quinta Helmer, Christian Hengstenberg, Oddgeir Holmen, Jouke-Jan Hottenga, Alan L James, Janina M Jeff, Åsa Johansson, Jennifer Jolley, Thorhildur Juliusdottir, Leena Kinnunen, Wolfgang Koenig, Markku Koskenvuo, Wolfgang Kratzer, Jaana Laitinen, Claudia Lamina, Karin Leander, Nanette R Lee, Peter Lichtner, Lars Lind, Jaana Lindström, Ken Sin Lo, Stéphane Lobbens, Roberto Lorbeer, Yingchang Lu, François Mach, Patrik K E Magnusson, Anubha Mahajan, Wendy L McArdle, Stela McLachlan, Cristina Menni, Sigrun Merger, Evelin Mihailov, Lili Milani, Alireza Moayyeri, Keri L Monda, Mario A Morken, Antonella Mulas, Gabriele Müller, Martina Müller-Nurasyid, Arthur W Musk, Ramaiah Nagaraja, Markus M Nöthen, Ilja M Nolte, Stefan Pilz, Nigel W Rayner, Frida Renstrom, Rainer Rettig, Janina S Ried, Stephan Ripke, Neil R Robertson, Lynda M Rose, Serena Sanna, Hubert Scharnagl, Salome Scholtens, Fredrick R Schumacher, William R Scott, Thomas Seufferlein, Jianxin Shi, Albert Vernon Smith, Joanna Smolonska, Alice V Stanton, Valgerdur Steinthorsdottir, Kathleen Stirrups, Heather M Stringham, Johan Sundström, Morris A Swertz, Amy J Swift, Ann-Christine Syvänen, Sian-Tsung Tan, Bamidele O Tayo, Barbara Thorand, Gudmar Thorleifsson, Jonathan P Tyrer, Hae-Won Uh, Liesbeth Vandenput, Frank C Verhulst, Sita H Vermeulen, Niek Verweij, Judith M Vonk, Lindsay L Waite, Helen R Warren, Dawn Waterworth, Michael N Weedon, Lynne R Wilkens, Christina Willenborg, Tom Wilsgaard, Mary K Wojczynski, Andrew Wong, Alan F Wright, Qunyuan Zhang, - -, Eoin P Brennan, Murim Choi, Zari Dastani, Alexander W Drong, Per Eriksson, Anders Franco-Cereceda, Jesper R Gådin, Ali G Gharavi, Michael E Goddard, Robert E Handsaker, Jinyan Huang, Fredrik Karpe, Sekar Kathiresan, Sarah Keildson, Krzysztof Kiryluk, Michiaki Kubo, Jong-Young Lee, Liming Liang, Richard P Lifton, Baoshan Ma, Steven A McCarroll, Amy J McKnight, Josine L Min, Miriam F Moffatt, Grant W Montgomery, Joanne M Murabito, George Nicholson, Dale R Nyholt, Yukinori Okada, John R B Perry, Rajkumar Dorajoo, Eva Reinmaa, Rany M Salem, Niina Sandholm, Robert A Scott, Lisette Stolk, Atsushi Takahashi, Toshihiro Tanaka, Ferdinand M Van't Hooft, Anna A E Vinkhuyzen, Harm-Jan Westra, Wei Zheng, Krina T Zondervan, Andrew C Heath, Dominique Arveiler, Stephan J L Bakker, John Beilby, Richard N Bergman, John Blangero, Pascal Bovet, Harry Campbell, Mark J Caulfield, Giancarlo Cesana, Aravinda Chakravarti, Daniel I Chasman, Peter S Chines, Francis S Collins, Dana C Crawford, L Adrienne Cupples, Daniele Cusi, John Danesh, Ulf de Faire, Hester M den Ruijter, Anna F Dominiczak, Raimund Erbel, Jeanette Erdmann, Johan G Eriksson, Martin Farrall, Stephan B Felix, Ele Ferrannini, Jean Ferrières, Ian Ford, Nita G Forouhi, Terrence Forrester, Oscar H Franco, Ron T Gansevoort, Pablo V Gejman, Christian Gieger, Omri Gottesman, Vilmundur Gudnason, Ulf Gyllensten, Alistair S Hall, Tamara B Harris, Andrew T Hattersley, Andrew A Hicks, Lucia A Hindorff, Aroon D Hingorani, Albert Hofman, Georg Homuth, G Kees Hovingh, Steve E Humphries, Steven C Hunt, Elina Hyppönen, Thomas Illig, Kevin B Jacobs, Marjo-Riitta Jarvelin, Karl-Heinz Jöckel, Berit Johansen, Pekka Jousilahti, J Wouter Jukema, Antti M Jula, Jaakko Kaprio, John J P Kastelein, Sirkka M Keinanen-Kiukaanniemi, Lambertus A Kiemeney, Paul Knekt, Jaspal S Kooner, Charles Kooperberg, Peter Kovacs, Aldi T Kraja, Meena Kumari, Johanna Kuusisto, Timo A Lakka, Claudia Langenberg, Loic Le Marchand, Terho Lehtimäki, Valeriya Lyssenko, Satu Männistö, André Marette, Tara C Matise, Colin A McKenzie, Barbara McKnight, Frans L Moll, Andrew D Morris, Andrew P Morris, Jeffrey C Murray, Mari Nelis, Claes Ohlsson, Albertine J Oldehinkel, Ken K Ong, Pamela A F Madden, Gerard Pasterkamp, John F Peden, Annette Peters, Dirkje S Postma, Peter P Pramstaller, Jackie F Price, Lu Qi, Olli T Raitakari, Tuomo Rankinen, D C Rao, Treva K Rice, Paul M Ridker, John D Rioux, Marylyn D Ritchie, Igor Rudan, Veikko Salomaa, Nilesh J Samani, Jouko Saramies, Mark A Sarzynski, Heribert Schunkert, Peter E H Schwarz, Peter Sever, Alan R Shuldiner, Juha Sinisalo, Ronald P Stolk, Konstantin Strauch, Anke Tönjes, David-Alexandre Trégouët, Angelo Tremblay, Elena Tremoli, Jarmo Virtamo, Marie-Claude Vohl, Uwe Völker, Gérard Waeber, Gonneke Willemsen, Jacqueline C Witteman, M Carola Zillikens, Linda S Adair, Philippe Amouyel, Folkert W Asselbergs, Themistocles L Assimes, Murielle Bochud, Bernhard O Boehm, Eric Boerwinkle, Stefan R Bornstein, Erwin P Bottinger, Claude Bouchard, Stéphane Cauchi, John C Chambers, Stephen J Chanock, Richard S Cooper, Paul I W de Bakker, George Dedoussis, Luigi Ferrucci, Paul W Franks, Philippe Froguel, Leif C Groop, Christopher A Haiman, Anders Hamsten, Jennie Hui, David J Hunter, Kristian Hveem, Robert C Kaplan, Mika Kivimaki, Diana Kuh, Markku Laakso, Yongmei Liu, Nicholas G Martin, Winfried März, Mads Melbye, Andres Metspalu, Susanne Moebus, Patricia B Munroe, Inger Njølstad, Ben A Oostra, Colin N A Palmer, Nancy L Pedersen, Markus Perola, Louis Pérusse, Ulrike Peters, Chris Power, Thomas Quertermous, Rainer Rauramaa, Fernando Rivadeneira, Timo E Saaristo, Danish Saleheen, Naveed Sattar, Eric E Schadt, David Schlessinger, P Eline Slagboom, Harold Snieder, Tim D Spector, Unnur Thorsteinsdottir, Michael Stumvoll, Jaakko Tuomilehto, André G Uitterlinden, Matti Uusitupa, Pim van der Harst, Mark Walker, Henri Wallaschofski, Nicholas J Wareham, Hugh Watkins, David R Weir, H-Erich Wichmann, James F Wilson, Pieter Zanen, Ingrid B Borecki, Panos Deloukas, Caroline S Fox, Iris M Heid, Jeffrey R O'Connell, David P Strachan, Kari Stefansson, Cornelia M van Duijn, Gonçalo R Abecasis, Lude Franke, Timothy M Frayling, Mark I McCarthy, Peter M Visscher, André Scherag, Cristen J Willer, Michael Boehnke, Karen L Mohlke, Cecilia M Lindgren, Jacques S Beckmann, Inês Barroso, Kari E North, Erik Ingelsson, Joel N Hirschhorn, Ruth J F Loos, Elizabeth K Speliotes
Year of publication:
2015
Volume:
518
Issue:
7538
Issn:
0028-0836
Journal title abbreviated:
NATURE
Journal title long:
Nature : a weekly illustrated journal of science
Impact factor:
38.138
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.