作者
Ruth JF Loos, Cecilia M Lindgren, Shengxu Li, Eleanor Wheeler, Jing Hua Zhao, Inga Prokopenko, Michael Inouye, Rachel M Freathy, Antony P Attwood, Jacques S Beckmann, Sonja I Berndt, Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening Trial Jacobs Kevin B 53 Chanock Stephen J 11 54 Hayes Richard B 11, Sven Bergmann, Amanda J Bennett, Sheila A Bingham, Murielle Bochud, Morris Brown, Stéphane Cauchi, John M Connell, Cyrus Cooper, George Davey Smith, Ian Day, Christian Dina, Subhajyoti De, Emmanouil T Dermitzakis, Alex SF Doney, Katherine S Elliott, Paul Elliott, David M Evans, I Sadaf Farooqi, Philippe Froguel, Jilur Ghori, Christopher J Groves, Rhian Gwilliam, David Hadley, Alistair S Hall, Andrew T Hattersley, Johannes Hebebrand, Iris M Heid, KORA Lamina Claudia 29 Gieger Christian 29 30 Illig Thomas 29 Meitinger Thomas 55 56 Wichmann H-Erich 29 30, Blanca Herrera, Anke Hinney, Sarah E Hunt, Marjo-Riitta Jarvelin, Toby Johnson, Jennifer DM Jolley, Fredrik Karpe, Andrew Keniry, Kay-Tee Khaw, Robert N Luben, Massimo Mangino, Jonathan Marchini, Wendy L McArdle, Ralph McGinnis, David Meyre, Patricia B Munroe, Andrew D Morris, Andrew R Ness, Matthew J Neville, Alexandra C Nica, Ken K Ong, Stephen O'Rahilly, Katharine R Owen, Colin NA Palmer, Konstantinos Papadakis, Simon Potter, Anneli Pouta, Lu Qi, Nurses' Health Study Kraft Peter 57 Hankinson Susan E 58 Hunter David J 40 44 57 58 Hu Frank B 40 58, Joshua C Randall, Nigel W Rayner, Susan M Ring, Manjinder S Sandhu, André Scherag, Matthew A Sims, Kijoung Song, Nicole Soranzo, Elizabeth K Speliotes, Diabetes Genetics Initiative Lyon Helen N 44 48 50 Voight Benjamin F 44 59 60 61 Ridderstrale Martin 62 Groop Leif 62 63, Holly E Syddall, Sarah A Teichmann, Nicholas J Timpson, Jonathan H Tobias, Manuela Uda, SardiNIA Study Scheet Paul 64 Sanna Serena 46 Abecasis Goncalo R 64 Albai Giuseppe 46 Nagaraja Ramaiah 65 Schlessinger David 65, Carla I Ganz Vogel, Chris Wallace, Dawn M Waterworth, Michael N Weedon, Wellcome Trust Case Control Consortium, Cristen J Willer, FUSION Jackson Anne U 47 Tuomilehto Jaakko 66 66 68 Collins Francis S 69 Boehnke Michael 47 Mohlke Karen L 70, Vicki L Wraight, Xin Yuan, Eleftheria Zeggini, Joel N Hirschhorn, David P Strachan, Willem H Ouwehand, Mark J Caulfield, Nilesh J Samani, Timothy M Frayling, Peter Vollenweider, Gerard Waeber, Vincent Mooser, Panos Deloukas, Mark I McCarthy, Nicholas J Wareham, Inês Barroso
发表日期
2008/6
期刊
Nature genetics
卷号
40
期号
6
页码范围
768-775
出版商
Nature Publishing Group US
简介
To identify common variants influencing body mass index (BMI), we analyzed genome-wide association data from 16,876 individuals of European descent. After previously reported variants in FTO, the strongest association signal (rs17782313, P = 2.9 × 10−6) mapped 188 kb downstream of MC4R (melanocortin-4 receptor), mutations of which are the leading cause of monogenic severe childhood-onset obesity. We confirmed the BMI association in 60,352 adults (per-allele effect = 0.05 Z-score units; P = 2.8 × 10−15) and 5,988 children aged 7–11 (0.13 Z-score units; P = 1.5 × 10−8). In case-control analyses (n = 10,583), the odds for severe childhood obesity reached 1.30 (P = 8.0 × 10−11). Furthermore, we observed overtransmission of the risk allele to obese offspring in 660 families (P (pedigree disequilibrium test average; PDT-avg) = 2.4 × 10−4). The SNP location and patterns of phenotypic associations are …
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RJF Loos, CM Lindgren, S Li, E Wheeler, JH Zhao… - Nature genetics, 2008