Association analyses of 249,796 individuals reveal 18 new loci associated with body mass index
Author(s)
Type
Journal Article
Abstract
Obesity is globally prevalent and highly heritable, but its underlying genetic factors remain largely elusive. To identify genetic loci for obesity susceptibility, we examined associations between body mass index and approximately 2.8 million SNPs in up to 123,865 individuals with targeted follow up of 42 SNPs in up to 125,931 additional individuals. We confirmed 14 known obesity susceptibility loci and identified 18 new loci associated with body mass index (P < 5 x 10(-)(8)), one of which includes a copy number variant near GPRC5B. Some loci (at MC4R, POMC, SH2B1 and BDNF) map near key hypothalamic regulators of energy balance, and one of these loci is near GIPR, an incretin receptor. Furthermore, genes in other newly associated loci may provide new insights into human body weight regulation.
Date Issued
2010-10-10
Date Acceptance
2010-09-15
Citation
Nature Genetics, 2010, 42, pp.937-948
ISSN
1546-1718
Publisher
Nature Publishing Group
Start Page
937
End Page
948
Journal / Book Title
Nature Genetics
Volume
42
Copyright Statement
© 2010, Rights Managed by Nature Publishing Group
Sponsor
Medical Research Council (MRC)
Medical Research Council (MRC)
Medical Research Council (MRC)
Grant Number
G0600331
G0801056B
G0801056/1
Subjects
Body Height/*genetics *Body Mass Index Body Size/genetics Body Weight/*genetics *Chromosome Mapping European Continental Ancestry Group/genetics Genetic Predisposition to Disease/genetics Genome-Wide Association Study Humans Obesity/genetics Polymorphism, Single Nucleotide
Notes
Speliotes, Elizabeth K Willer, Cristen J Berndt, Sonja I Monda, Keri L Thorleifsson, Gudmar Jackson, Anne U Lango Allen, Hana Lindgren, Cecilia M Luan, Jian'an Magi, Reedik Randall, Joshua C Vedantam, Sailaja Winkler, Thomas W Qi, Lu Workalemahu, Tsegaselassie Heid, Iris M Steinthorsdottir, Valgerdur Stringham, Heather M Weedon, Michael N Wheeler, Eleanor Wood, Andrew R Ferreira, Teresa Weyant, Robert J Segre, Ayellet V Estrada, Karol Liang, Liming Nemesh, James Park, Ju-Hyun Gustafsson, Stefan Kilpelainen, Tuomas O Yang, Jian Bouatia-Naji, Nabila Esko, Tonu Feitosa, Mary F Kutalik, Zoltan Mangino, Massimo Raychaudhuri, Soumya Scherag, Andre Smith, Albert Vernon Welch, Ryan Zhao, Jing Hua Aben, Katja K Absher, Devin M Amin, Najaf Dixon, Anna L Fisher, Eva Glazer, Nicole L Goddard, Michael E Heard-Costa, Nancy L Hoesel, Volker Hottenga, Jouke-Jan Johansson, Asa Johnson, Toby Ketkar, Shamika Lamina, Claudia Li, Shengxu Moffatt, Miriam F Myers, Richard H Narisu, Narisu Perry, John R B Peters, Marjolein J Preuss, Michael Ripatti, Samuli Rivadeneira, Fernando Sandholt, Camilla Scott, Laura J Timpson, Nicholas J Tyrer, Jonathan P van Wingerden, Sophie Watanabe, Richard M White, Charles C Wiklund, Fredrik Barlassina, Christina Chasman, Daniel I Cooper, Matthew N Jansson, John-Olov Lawrence, Robert W Pellikka, Niina Prokopenko, Inga Shi, Jianxin Thiering, Elisabeth Alavere, Helene Alibrandi, Maria T S Almgren, Peter Arnold, Alice M Aspelund, Thor Atwood, Larry D Balkau, Beverley Balmforth, Anthony J Bennett, Amanda J Ben-Shlomo, Yoav Bergman, Richard N Bergmann, Sven Biebermann, Heike Blakemore, Alexandra I F Boes, Tanja Bonnycastle, Lori L Bornstein, Stefan R Brown, Morris J Buchanan, Thomas A Busonero, Fabio Campbell, Harry Cappuccio, Francesco P Cavalcanti-Proenca, Christine Chen, Yii-Der Ida Chen, Chih-Mei Chines, Peter S Clarke, Robert Coin, Lachlan Connell, John Day, Ian N M den Heijer, Martin Duan, Jubao Ebrahim, Shah Elliott, Paul Elosua, Roberto Eiriksdottir, Gudny Erdos, Michael R Eriksson, Johan G Facheris, Maurizio F Felix, Stephan B Fischer-Posovszky, Pamela Folsom, Aaron R Friedrich, Nele Freimer, Nelson B Fu, Mao Gaget, Stefan Gejman, Pablo V Geus, Eco J C Gieger, Christian Gjesing, Anette P Goel, Anuj Goyette, Philippe Grallert, Harald Grassler, Jurgen Greenawalt, Danielle M Groves, Christopher J Gudnason, Vilmundur Guiducci, Candace Hartikainen, Anna-Liisa Hassanali, Neelam Hall, Alistair S Havulinna, Aki S Hayward, Caroline Heath, Andrew C Hengstenberg, Christian Hicks, Andrew A Hinney, Anke Hofman, Albert Homuth, Georg Hui, Jennie Igl, Wilmar Iribarren, Carlos Isomaa, Bo Jacobs, Kevin B Jarick, Ivonne Jewell, Elizabeth John, Ulrich Jorgensen, Torben Jousilahti, Pekka Jula, Antti Kaakinen, Marika Kajantie, Eero Kaplan, Lee M Kathiresan, Sekar Kettunen, Johannes Kinnunen, Leena Knowles, Joshua W Kolcic, Ivana Konig, Inke R Koskinen, Seppo Kovacs, Peter Kuusisto, Johanna Kraft, Peter Kvaloy, Kirsti Laitinen, Jaana Lantieri, Olivier Lanzani, Chiara Launer, Lenore J Lecoeur, Cecile Lehtimaki, Terho Lettre, Guillaume Liu, Jianjun Lokki, Marja-Liisa Lorentzon, Mattias Luben, Robert N Ludwig, Barbara Magic Manunta, Paolo Marek, Diana Marre, Michel Martin, Nicholas G McArdle, Wendy L McCarthy, Anne McKnight, Barbara Meitinger, Thomas Melander, Olle Meyre, David Midthjell, Kristian Montgomery, Grant W Morken, Mario A Morris, Andrew P Mulic, Rosanda Ngwa, Julius S Nelis, Mari Neville, Matt J Nyholt, Dale R O'Donnell, Christopher J O'Rahilly, Stephen Ong, Ken K Oostra, Ben Pare, Guillaume Parker, Alex N Perola, Markus Pichler, Irene Pietilainen, Kirsi H Platou, Carl G P Polasek, Ozren Pouta, Anneli Rafelt, Suzanne Raitakari, Olli Rayner, Nigel W Ridderstrale, Martin Rief, Winfried Ruokonen, Aimo Robertson, Neil R Rzehak, Peter Salomaa, Veikko Sanders, Alan R Sandhu, Manjinder S Sanna, Serena Saramies, Jouko Savolainen, Markku J Scherag, Susann Schipf, Sabine Schreiber, Stefan Schunkert, Heribert Silander, Kaisa Sinisalo, 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Epub 2010 Oct 10. Obesity is globally prevalent and highly heritable, but its underlying genetic factors remain largely elusive. To identify genetic loci for obesity susceptibility, we examined associations between body mass index and approximately 2.8 million SNPs in up to 123,865 individuals with targeted follow up of 42 SNPs in up to 125,931 additional individuals. We confirmed 14 known obesity susceptibility loci and identified 18 new loci associated with body mass index (P < 5 x 10(-)(8)), one of which includes a copy number variant near GPRC5B. Some loci (at MC4R, POMC, SH2B1 and BDNF) map near key hypothalamic regulators of energy balance, and one of these loci is near GIPR, an incretin receptor. Furthermore, genes in other newly associated loci may provide new insights into human body weight regulation.
Publication Status
Published