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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).

Original publication

DOI

10.1038/ng.2247

Type

Journal article

Journal

Nature genetics

Publication Date

05/2012

Volume

44

Pages

526 - 531

Addresses

Center for Applied Genomics, Abramson Research Center, The Children’s Hospital of Philadelphia, Philadelphia, Pennsylvania, USA.

Keywords

Early Growth Genetics Consortium, Humans, Obesity, Genetic Predisposition to Disease, Genetic Markers, Body Mass Index, Case-Control Studies, Polymorphism, Single Nucleotide, Adolescent, Adult, Genome-Wide Association Study, Young Adult, Genetic Loci