Six new loci associated with body mass index highlight a neuronal influence on body weight regulation

doi:10.1038/ng.287

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Six new loci associated with body mass index highlight a neuronal influence on body weight regulation

Cristen J Willer, Elizabeth K Speliotes, Ruth J F Loos, Shengxu Li, Cecilia M Lindgren, Iris M Heid, Sonja I Berndt, Amanda L Elliott, Anne U Jackson, Claudia Lamina, Guillaume Lettre, Noha Lim, Helen N Lyon, Steven A McCarroll, Konstantinos Papadakis, Lu Qi, Joshua C Randall, Rosa Maria Roccasecca, Serena Sanna, Paul Scheet, Michael N Weedon, Eleanor Wheeler, Jing Hua Zhao, Leonie C Jacobs, Inga Prokopenko, Nicole Soranzo, Toshiko Tanaka, Nicholas J Timpson, Peter Almgren, Amanda Bennett, Richard N Bergman, Sheila A Bingham, Lori L Bonnycastle, Morris Brown, Noël P Burtt, Peter Chines, Lachlan Coin, Francis S Collins, John M Connell, Cyrus Cooper, George Davey Smith, Elaine M Dennison, Parimal Deodhar, Paul Elliott, Michael R Erdos, Karol Estrada, David M Evans, Lauren Gianniny, Christian Gieger, Christopher J Gillson, Candace Guiducci, Rachel Hackett, David Hadley, Alistair S Hall, Aki S Havulinna, Johannes Hebebrand, Albert Hofman, Bo Isomaa, Kevin B Jacobs, Toby Johnson, Pekka Jousilahti, Zorica Jovanovic, Kay-Tee Khaw, Peter Kraft, Mikko Kuokkanen, Johanna Kuusisto, Jaana Laitinen, Edward G Lakatta, Jian'an Luan, Robert N Luben, Massimo Mangino, Wendy L McArdle, Thomas Meitinger, Antonella Mulas, Patricia B Munroe, Narisu Narisu, Andrew R Ness, Kate Northstone, Stephen O'Rahilly, Carolin Purmann, Matthew G Rees, Martin Ridderstråle, Susan M Ring, Fernando Rivadeneira, Aimo Ruokonen, Manjinder S Sandhu, Jouko Saramies, Laura J Scott, Angelo Scuteri, Kaisa Silander, Matthew A Sims, Kijoung Song, Jonathan Stephens, Suzanne Stevens, Heather M Stringham, Y C Loraine Tung, Timo T Valle, Cornelia M Van Duijn, Karani S Vimaleswaran, Peter Vollenweider, Gerard Waeber, Chris Wallace, Richard M Watanabe, Dawn M Waterworth, Nicholas Watkins, Jacqueline C M Witteman, Eleftheria Zeggini, Guangju Zhai, M Carola Zillikens, David Altshuler, Mark J Caulfield, Stephen J Chanock, I Sadaf Farooqi, Luigi Ferrucci, Jack M Guralnik, Andrew T Hattersley, Frank B Hu, Marjo-Riitta Jarvelin, Markku Laakso, Vincent Mooser, Ken K Ong, Willem H Ouwehand, Veikko Salomaa, Nilesh J Samani, Timothy D Spector, Tiinamaija Tuomi, Jaakko Tuomilehto, Manuela Uda, André G Uitterlinden, Nicholas J Wareham, Panagiotis Deloukas, Timothy M Frayling, Leif C Groop, Richard B Hayes, David J Hunter, Karen L Mohlke, Leena Peltonen, David Schlessinger, David P Strachan, H-Erich Wichmann, Mark I McCarthy, Michael Boehnke, Inês Barroso, Gonçalo R Abecasis and Joel N Hirschhorn Nat Genet 41(1):25-34 (2008) PMID 19079261 PMCID: PMC2695662

Common variants at only two loci, FTO and MC4R, have been reproducibly associated with body mass index (BMI) in humans. To identify additional loci, we conducted meta-analysis of 15 genome-wide association studies for BMI (n > 32,000) and followed up top signals in 14 additional cohorts (n > 59,000). We strongly confirm FTO and MC4R and identify six additional loci (P < 5 x 10(-8)): TMEM18, KCTD15, GNPDA2, SH2B1, MTCH2 and NEGR1 (where a 45-kb deletion polymorphism is a candidate causal variant). Several of the likely causal genes are highly expressed or known to act in the central nervous system (CNS), emphasizing, as in rare monogenic forms of obesity, the role of the CNS in predisposition to obesity.

DOI: 10.1038/ng.287
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