Six new loci associated with body mass index highlight a neuronal influence on body weight regulation by Willer Cristen J, Speliotes Elizabeth K, Loos Ruth J F, Li Shengxu, Lindgren Cecilia M, Heid Iris M, Berndt Sonja I, Elliott Amanda L, Jackson Anne U, Lamina Claudia, Lettre Guillaume, Lim Noha, Lyon Helen N, McCarroll Steven A, Papadakis Konstantinos, Qi Lu, Randall Joshua C, Roccasecca Rosa Maria, Sanna Serena, Scheet Paul, Weedon Michael N, Wheeler Eleanor, Zhao Jing Hua, Jacobs Leonie C, Prokopenko Inga, Soranzo Nicole, Tanaka Toshiko, Timpson Nicholas J, Almgren Peter, Bennett Amanda, Bergman Richard N, Bingham Sheila A, Bonnycastle Lori L, Brown Morris, Burtt Noël P, Chines Peter, Coin Lachlan, Collins Francis S, Connell John M, Cooper Cyrus, Smith George Davey, Dennison Elaine M, Deodhar Parimal, Elliott Paul, Erdos Michael R, Estrada Karol, Evans David M, Gianniny Lauren, Gieger Christian, Gillson Christopher J, Guiducci Candace, Hackett Rachel, Hadley David, Hall Alistair S, Havulinna Aki S, Hebebrand Johannes, Hofman Albert, Isomaa Bo, Jacobs Kevin B, Johnson Toby, Jousilahti Pekka, Jovanovic Zorica, Khaw Kay-Tee, Kraft Peter, Kuokkanen Mikko, Kuusisto Johanna, Laitinen Jaana, Lakatta Edward G, Luan Jian'an, Luben Robert N, Mangino Massimo, McArdle Wendy L, Meitinger Thomas, Mulas Antonella, Munroe Patricia B, Narisu Narisu, Ness Andrew R, Northstone Kate, O'Rahilly Stephen, Purmann Carolin, Rees Matthew G, Ridderstråle Martin, Ring Susan M, Rivadeneira Fernando, Ruokonen Aimo, Sandhu Manjinder S, Saramies Jouko, Scott Laura J, Scuteri Angelo, Silander Kaisa, Sims Matthew A, Song Kijoung, Stephens Jonathan, Stevens Suzanne, Stringham Heather M, Tung Y C Loraine, Valle Timo T, Van Duijn Cornelia M, Vimaleswaran Karani S, Vollenweider Peter, Waeber Gerard, Wallace Chris, Watanabe Richard M, Waterworth Dawn M, Watkins Nicholas, Wellcome Trust Case Control Consortium, Witteman Jacqueline C M, Zeggini Eleftheria, Zhai Guangju, Zillikens M Carola, Altshuler David, Caulfield Mark J, Chanock Stephen J, Farooqi I Sadaf, Ferrucci Luigi, Guralnik Jack M, Hattersley Andrew T, Hu Frank B, Jarvelin Marjo-Riitta, Laakso Markku, Mooser Vincent, Ong Ken K, Ouwehand Willem H, Salomaa Veikko, Samani Nilesh J, Spector Timothy D, Tuomi Tiinamaija, Tuomilehto Jaakko, Uda Manuela, Uitterlinden André G, Wareham Nicholas J, Deloukas Panagiotis, Frayling Timothy M, Groop Leif C, Hayes Richard B, Hunter David J, Mohlke Karen L, Peltonen Leena, Schlessinger David, Strachan David P, Wichmann H-Erich, McCarthy Mark I, Boehnke Michael, Barroso Inês, Abecasis Gonçalo R, Hirschhorn Joel N, Genetic Investigation of ANthropometric Traits Consortium in Nature genetics (2009). PubMed

Abstract

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.

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