Genome‐wide association study of height‐adjusted BMI in childhood identifies functional variant in ADCY3. (21st July 2014)

• Record Type: Journal Article
• Authors: Stergiakouli, Evangelia; Gaillard, Romy; Tavaré, Jeremy M.; Balthasar, Nina; Loos, Ruth J.; Taal, Hendrik R.; Evans, David M.; Rivadeneira, Fernando; St Pourcain, Beate; Uitterlinden, André G.; Kemp, John P.; Hofman, Albert; Ring, Susan M.; Cole, Tim J.; Jaddoe, Vincent W.V.; Davey Smith, George; Timpson, Nicholas J.
• Is Part Of: Obesity. Volume 22:Number 10(2014:Oct.)
• Page Start: 2252
• Page End: 2259
• Publication Date: 2014-07-21
• Subjects: Obesity -- Periodicals; 616.398005
• DOI: 10.1002/oby.20840
• Languages: English
• ISSNs: 1930-7381

Abstract

<abstract abstract-type="main"> <title> <x xml:space="preserve">Abstract</x> </title> <sec id="oby20840-sec-0001" sec-type="section"> <title>Objective</title> <p>Genome‐wide association studies (GWAS) of BMI are mostly undertaken under the assumption that "kg/m<sup>2</sup>" is an index of weight fully adjusted for height, but in general this is not true. The aim here was to assess the contribution of common genetic variation to a adjusted version of that phenotype which appropriately accounts for covariation in height in children.</p> </sec> <sec id="oby20840-sec-0002" sec-type="section"> <title>Methods</title> <p>A GWAS of height‐adjusted BMI (BMI[<italic>x</italic>] = weight/height<sup>x</sup>), calculated to be uncorrelated with height, in 5809 participants (mean age 9.9 years) from the Avon Longitudinal Study of Parents and Children (ALSPAC) was performed.</p> </sec> <sec id="oby20840-sec-0003" sec-type="section"> <title>Results</title> <p>GWAS based on BMI[<italic>x</italic>] yielded marked differences in genomewide results profile. SNPs in <italic>ADCY3</italic> (adenylate cyclase 3) were associated at genome‐wide significance level (rs11676272 (0.28 kg/m<sup>3.1</sup> change per allele G (0.19, 0.38), <italic>P</italic> = 6 × 10<sup>−9</sup>). In contrast, they showed marginal evidence of association with conventional BMI [rs11676272 (0.25 kg/m<sup>2</sup> (0.15, 0.35), <italic>P</italic> = 6 × 10<sup>−7</sup>)]. Results were replicated in an independent sample, the Generation R study.</p> </sec> <sec id="oby20840-sec-0004" sec-type="section"> <title>Conclusions</title> <p>Analysis of BMI[<italic>x</italic>] showed differences to that of conventional BMI. The association signal at <italic>ADCY3</italic> appeared to be driven by a missense variant and it was strongly correlated with expression of this gene. Our work highlights the importance of well understood phenotype use (and the danger of convention) in characterising genetic contributions to complex traits.</p> </sec> </abstract>