六个与体重指数相关的新基因座凸显了神经元对体重调节的影响。
Six new loci associated with body mass index highlight a neuronal influence on body weight regulation.
作者信息
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, 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
机构信息
Genetic Investigation of ANthropometric Traits Consortium.
出版信息
Nat Genet. 2009 Jan;41(1):25-34. doi: 10.1038/ng.287. Epub 2008 Dec 14.
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.
在人类中，仅有两个基因座（FTO和MC4R）的常见变异已被反复证实与体重指数（BMI）相关。为了识别其他基因座，我们对15项关于BMI的全基因组关联研究（样本量n>32000）进行了荟萃分析，并在另外14个队列（样本量n>59000）中对前几位的信号进行了跟进研究。我们有力地证实了FTO和MC4R基因座，并识别出另外六个基因座（P<5×10⁻⁸）：TMEM18、KCTD15、GNPDA2、SH2B1、MTCH2和NEGR1（其中一个45kb的缺失多态性是候选因果变异）。几个可能的因果基因在中枢神经系统（CNS）中高表达或已知在其中发挥作用，这正如在罕见的单基因肥胖形式中一样，强调了中枢神经系统在肥胖易感性中的作用。
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