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PLoS One. 2011 Apr 28;6(4):e18939. doi: 10.1371/journal.pone.0018939.

A genome-wide association study on obesity and obesity-related traits.

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  • 1Center for Applied Genomics, Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, United States of America.

Erratum in

  • PLoS One. 2012;7(2). doi: 10.1371/annotation/a34ee94e-3e6a-48bd-a19e-398a4bb88580.

Abstract

Large-scale genome-wide association studies (GWAS) have identified many loci associated with body mass index (BMI), but few studies focused on obesity as a binary trait. Here we report the results of a GWAS and candidate SNP genotyping study of obesity, including extremely obese cases and never overweight controls as well as families segregating extreme obesity and thinness. We first performed a GWAS on 520 cases (BMI>35 kg/m(2)) and 540 control subjects (BMI<25 kg/m(2)), on measures of obesity and obesity-related traits. We subsequently followed up obesity-associated signals by genotyping the top ∼500 SNPs from GWAS in the combined sample of cases, controls and family members totaling 2,256 individuals. For the binary trait of obesity, we found 16 genome-wide significant signals within the FTO gene (strongest signal at rs17817449, P = 2.5 × 10(-12)). We next examined obesity-related quantitative traits (such as total body weight, waist circumference and waist to hip ratio), and detected genome-wide significant signals between waist to hip ratio and NRXN3 (rs11624704, P = 2.67 × 10(-9)), previously associated with body weight and fat distribution. Our study demonstrated how a relatively small sample ascertained through extreme phenotypes can detect genuine associations in a GWAS.

PMID:
21552555
[PubMed - indexed for MEDLINE]
PMCID:
PMC3084240
Free PMC Article
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