Genome-Wide Association Scan Meta-Analysis Identifies Three Loci Influencing Adiposity and Fat Distribution

Wellcome Trust Centre for Human Genetics, University of Oxford, , Oxford, United Kingdom.
PLoS Genetics (Impact Factor: 7.53). 07/2009; 5(6):e1000508. DOI: 10.1371/journal.pgen.1000508
Source: PubMed


To identify genetic loci influencing central obesity and fat distribution, we performed a meta-analysis of 16 genome-wide association studies (GWAS, N = 38,580) informative for adult waist circumference (WC) and waist-hip ratio (WHR). We selected 26 SNPs for follow-up, for which the evidence of association with measures of central adiposity (WC and/or WHR) was strong and disproportionate to that for overall adiposity or height. Follow-up studies in a maximum of 70,689 individuals identified two loci strongly associated with measures of central adiposity; these map near TFAP2B (WC, P = 1.9x10(-11)) and MSRA (WC, P = 8.9x10(-9)). A third locus, near LYPLAL1, was associated with WHR in women only (P = 2.6x10(-8)). The variants near TFAP2B appear to influence central adiposity through an effect on overall obesity/fat-mass, whereas LYPLAL1 displays a strong female-only association with fat distribution. By focusing on anthropometric measures of central obesity and fat distribution, we have identified three loci implicated in the regulation of human adiposity.

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Available from: Dawn M Waterworth, Oct 08, 2015
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    • "While APOE ε3 compared to ε4 has been associated with higher BMI and body weight in children and adults [33] [34] [35] [36] [37], others found no significant differences [38] [39]. APOE genotype has not thus far emerged as a modulator of obesity measures such as abdominal fat, waist-to-hip ratio or BMI in large scale genome wide association studies (GWAS) [40] [41] [42] [43]. "
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    Molecular Nutrition & Food Research 11/2014; 59(2). DOI:10.1002/mnfr.201400636 · 4.60 Impact Factor
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    • "p < 1.53 × 10−6; see the electronic supplementary material, table S3) expressed in adipose tissue. The TFAP2B-rs987237 genetic variant has been previously associated with a number of metabolic disorders, including development of T2DM [21], BMI [22] and other BMI-related phenotypes such as waist circumference [4]. In addition, several SNPs localized within regions previously associated with BMI showed associations at a significance threshold of p < 0.001. "
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    Journal of The Royal Society Interface 02/2014; 11(94):20130908. DOI:10.1098/rsif.2013.0908 · 3.92 Impact Factor
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    • "The second case takes a bit more elaborate approach, where the results of two GWA studies for adiposity [24,25] were combined by the union (seven genes) of two hit gene lists (three and four genes respectively). Neither conventional nor simple cross-species GSA resulted in any significant GSA hits for phenotypic annotation. "
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