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

By 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. Va'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 Njolstad, 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, Goncalo 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, P D'Adamo and P Gasparini

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

Topics: 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
Year: 2015
DOI identifier: 10.1038/nature14177
OAI identifier: oai:arts.units.it:11368/2833807
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