Common variants near MC4R are associated with fat mass, weight and risk of obesity

RJF Loos; CM Lindgren; S Li; E Wheeler; J Hua Zhao; I Prokopenko; M Inouye; RM Freathy; AP Attwood; JS Beckmann; SI Berndt; S Bergmann; AJ Bennett; SA Bingham; M Bochud; M Brown; S Cauchi; JM Connell; C Cooper; G Davey Smith; I Day; C Dina; S De; ET Dermitzakis; ASF Doney; KS Elliott; P Elliott; DM Evans; I Sadaf Farooqi; P Froguel; J Ghori; CJ Groves; R Gwilliam; D Hadley; AS Hall; AT Hattersley; J Hebebrand; IM Heid; B Herrera; A Hinney; SE Hunt; MR Jarvelin; T Johnson; JDM Jolley; F Karpe; A Keniry; KT Khaw; RN Luben; M Mangino; J Marchini; WL McArdle; R McGinnis; D Meyre; PB Munroe; AD Morris; AR Ness; MJ Neville; AC Nica; KK Ong; S O'Rahilly; KR Owen; CNA Palmer; K Papadakis; S Potter; A Pouta; L Qi; JC Randall; NW Rayner; SM Ring; MS Sandhu; A Scherag; MA Sims; K Song; N Soranzo; EK Speliotes; HE Syddall; SA Teichmann; NJ Timpson; JH Tobias; M Uda; CI Ganz Vogel; C Wallace; DM Waterworth; MN Weedon; CJ Willer; VL Wraight; X Yuan; E Zeggini; JN Hirschhorn; DP Strachan; WH Ouwehand; MJ Caulfield; NJ Samani; TM Frayling; P Vollenweider; G Waeber; V Mooser; P Deloukas; MI McCarthy; NJ Wareham

Journal article

Common variants near MC4R are associated with fat mass, weight and risk of obesity

RJF Loos, CM Lindgren, S Li, E Wheeler, J Hua Zhao, I Prokopenko, M Inouye, RM Freathy, AP Attwood, JS Beckmann, SI Berndt, S Bergmann, AJ Bennett, SA Bingham, M Bochud, M Brown, S Cauchi, JM Connell, C Cooper, G Davey Smith Show all

Nature Genetics | Published : 2008

DOI: 10.1038/ng.140

Abstract

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..

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