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

Publication

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

Journal Paper/Review - Feb 12, 2015

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

Citation

Croteau-Chonka D, Bakker S, Esko T, Beilby J, Fall T, Bergman R, Ferreira T, Blangero J, Gustafsson S, Bovet P, Kutalik Z, Campbell H, Luan J, Caulfield M, Mägi R, Cesana G, Randall J, Chakravarti A, Chasman D, Wood A, Chines P, Collins F, Crawford D, Cupples L, Cusi D, Danesh J, de Faire U, den Ruijter H, Dominiczak A, Erbel R, Erdmann J, Eriksson J, Farrall M, Felix S, Ferrannini E, Ferrieres J, Ford I, Forouhi N, Forrester T, Deng G, Franco O, Ehret G, Gansevoort R, Feenstra B, Gejman P, Feitosa M, Gieger C, Fischer K, Gottesman O, Goel A, Gudnason V, Gong J, Gyllensten U, Jackson A, Hall A, Kanoni S, Harris T, Kleber M, Hattersley A, Kristiansson K, Hicks A, Lim U, Hindorff L, Lotay V, Hingorani A, Mangino M, Hofman A, Leach I, Homuth G, Medina-Gomez C, Hovingh G, Medland S, Humphries S, Nalls M, Hunt S, Palmer C, Hyppönen E, Pasko D, Illig T, Pechlivanis S, Jacobs K, Peters M, Jarvelin M, Prokopenko I, Jöckel K, Shungin D, Johansen B, Stančáková A, Jousilahti P, Strawbridge R, Jukema J, Sung Y, Jula A, Tanaka T, Kaprio J, Teumer A, Kastelein J, Trompet S, Keinanen-Kiukaanniemi S, van der Laan S, Kiemeney L, van Setten J, Knekt P, van Vliet-Ostaptchouk J, Kooner J, Wang Z, Kooperberg C, Yengo L, Kovacs P, Zhang W, Kraja A, Isaacs A, Kumari M, Albrecht E, Kuusisto J, Arnlöv J, Lakka T, Arscott G, Langenberg C, Attwood A, Marchand L, Bandinelli S, Lehtimäki T, Barrett A, Lyssenko V, Bas I, Männistö S, Bellis C, Marette A, Bennett A, Matise T, Berne C, McKenzie C, Blagieva R, McKnight B, Blüher M, Moll F, Böhringer S, Morris A, Bonnycastle L, Morris A, Böttcher Y, Murray J, Boyd H, Nelis M, Bruinenberg M, Ohlsson C, Caspersen I, Oldehinkel A, Chen Y, Ong K, Clarke R, Madden P, Daw E, Pasterkamp G, de Craen A, Peden J, Delgado G, Peters A, Dimitriou M, Postma D, Doney A, Pramstaller P, Eklund N, Price J, Estrada K, Qi L, Eury E, Raitakari O, Folkersen L, Rankinen T, Fraser R, Rao D, Garcia M, Rice T, Geller F, Ridker P, Giedraitis V, Rioux J, Gigante B, Ritchie M, Go A, Rudan I, Golay A, Salomaa V, Goodall A, Samani N, Gordon S, Saramies J, Gorski M, Sarzynski M, Grabe H, Schunkert H, Grallert H, Schwarz P, Grammer T, Sever P, Gräßler J, Shuldiner A, Grönberg H, Sinisalo J, Groves C, Stolk R, Gusto G, Strauch K, Haessler J, Tönjes A, Hall P, Trégouët D, Haller T, Tremblay A, Hallmans G, Tremoli E, Hartman C, Virtamo J, Hassinen M, Vohl M, Hayward C, Völker U, Heard-Costa N, Waeber G, Helmer Q, Willemsen G, Hengstenberg C, Witteman J, Holmen O, Zillikens M, Hottenga J, Adair L, James A, Amouyel P, Jeff J, Asselbergs F, Johansson Å, Assimes T, Jolley J, Bochud M, Juliusdottir T, Boehm B, Kinnunen L, Boerwinkle E, Koenig W, Bornstein S, Koskenvuo M, Bottinger E, Kratzer W, Bouchard C, Laitinen J, Cauchi S, Lamina C, Chambers J, Leander K, Chanock S, Lee N, Cooper R, Lichtner P, de Bakker P, Lind L, Dedoussis G, Lindström J, Ferrucci L, Lo K, Franks P, Lobbens S, Froguel P, Lorbeer R, Groop L, Lu Y, Haiman C, Mach F, Hamsten A, Magnusson P, Hui J, Mahajan A, Hunter D, McArdle W, Hveem K, McLachlan S, Kaplan R, Menni C, Kivimäki M, Merger S, Kuh D, Mihailov E, Laakso M, Milani L, Liu Y, Moayyeri A, Martin N, Monda K, März W, Morken M, Melbye M, Mulas A, Metspalu A, Müller G, Moebus S, Müller-Nurasyid M, Munroe P, Musk A, Njølstad I, Nagaraja R, Oostra B, Nöthen M, Palmer C, Nolte I, Pedersen N, Pilz S, Perola M, Rayner N, Pérusse L, Renström F, Peters U, Rettig R, Power C, Ried J, Quertermous T, Ripke S, Rauramaa R, Robertson N, Rivadeneira F, Rose L, Saaristo T, Sanna S, Saleheen D, Scharnagl H, Sattar N, Scholtens S, Schadt E, Schumacher F, Schlessinger D, Scott W, Slagboom P, Seufferlein T, Snieder H, Shi J, Spector T, Smith A, Thorsteinsdottir U, Smolonska J, Stumvoll M, Stanton A, Tuomilehto J, Steinthorsdottir V, Uitterlinden A, Stirrups K, Uusitupa M, Stringham H, van der Harst P, Sundstrom J, Walker M, Swertz M, Wallaschofski H, Swift A, Wareham N, Syvänen A, Watkins H, Tan S, Weir D, Tayo B, Wichmann H, Thorand B, Wilson J, Thorleifsson G, Zanen P, Tyrer J, Borecki I, Uh H, Deloukas P, Vandenput L, Fox C, Verhulst F, Heid I, Vermeulen S, O'Connell J, Verweij N, Strachan D, Vonk J, Stefansson K, Waite L, van Duijn C, Warren H, Abecasis G, Waterworth D, Franke L, Weedon M, Frayling T, Wilkens L, McCarthy M, Willenborg C, Visscher P, Wilsgaard T, Scherag A, Wojczynski M, Willer C, Wong A, Boehnke M, Wright A, Mohlke K, Zhang Q, Lindgren C, Beckmann J, Brennan E, Barroso I, Choi M, North K, Dastani Z, Ingelsson E, Drong A, Hirschhorn J, Eriksson P, Loos R, Franco-Cereceda A, Speliotes E, Gådin J, Gharavi A, Goddard M, Handsaker R, Huang J, Karpe F, Kathiresan S, Keildson S, Kiryluk K, Kubo M, Lee J, Liang L, Lifton R, Ma B, McCarroll S, McKnight A, Min J, Moffatt M, Montgomery G, Murabito J, Nicholson G, Nyholt D, Okada Y, Perry J, Dorajoo R, Reinmaa E, Salem R, Sandholm N, Scott R, Locke A, Stolk L, Kahali B, Takahashi A, Berndt S, Tanaka T, Justice A, van 't Hooft F, Pers T, Vinkhuyzen A, Day F, Westra H, Powell C, Zheng W, Vedantam S, Zondervan K, Buchkovich M, Heath A, Yang J, Arveiler D, Winkler T, Absher D, Amin N, Anderson D, Beekman M, Bolton J, Bragg-Gresham J, Buyske S, Demirkan A, Schmidt E, Karjalainen J, Workalemahu T, Faul J, Smith J, Zhao J, Zhao W, Chen J, Fehrmann R, Hedman Å. Genetic studies of body mass index yield new insights for obesity biology. Nature 2015; 518:197-206.

Type

Journal Paper/Review (English)

Journal

Nature 2015; 518

Publication Date

Feb 12, 2015

Issn Electronic

1476-4687

Pages

197-206

Brief description/objective

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.