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A genome-wide association meta-analysis identifies new childhood obesity loci
Authors:Bradfield Jonathan P  Taal H Rob  Timpson Nicholas J  Scherag André  Lecoeur Cecile  Warrington Nicole M  Hypponen Elina  Holst Claus  Valcarcel Beatriz  Thiering Elisabeth  Salem Rany M  Schumacher Fredrick R  Cousminer Diana L  Sleiman Patrick M A  Zhao Jianhua  Berkowitz Robert I  Vimaleswaran Karani S  Jarick Ivonne  Pennell Craig E  Evans David M  St Pourcain Beate  Berry Diane J  Mook-Kanamori Dennis O  Hofman Albert  Rivadeneira Fernando  Uitterlinden André G  van Duijn Cornelia M  van der Valk Ralf J P  de Jongste Johan C  Postma Dirkje S  Boomsma Dorret I  Gauderman W James  Hassanein Mohamed T  Lindgren Cecilia M
Affiliation:Center for Applied Genomics, Abramson Research Center, The Children’s Hospital of Philadelphia, Philadelphia, Pennsylvania, USA.
Abstract:
Multiple genetic variants have been associated with adult obesity and a few with severe obesity in childhood; however, less progress has been made in establishing genetic influences on common early-onset obesity. We performed a North American, Australian and European collaborative meta-analysis of 14 studies consisting of 5,530 cases (≥95th percentile of body mass index (BMI)) and 8,318 controls (<50th percentile of BMI) of European ancestry. Taking forward the eight newly discovered signals yielding association with P < 5 × 10(-6) in nine independent data sets (2,818 cases and 4,083 controls), we observed two loci that yielded genome-wide significant combined P values near OLFM4 at 13q14 (rs9568856; P = 1.82 × 10(-9); odds ratio (OR) = 1.22) and within HOXB5 at 17q21 (rs9299; P = 3.54 × 10(-9); OR = 1.14). Both loci continued to show association when two extreme childhood obesity cohorts were included (2,214 cases and 2,674 controls). These two loci also yielded directionally consistent associations in a previous meta-analysis of adult BMI(1).
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