Genome-wide association study of height-adjusted BMI in childhood identifies functional variant in ADCY3

Stergiakouli, Evangelia, Gaillard, Romy, Tavare, Jeremy M., Balthasar, Nina, Loos, Ruth J., Taal, Hendrik R., Evans, David M., Rivadeneira, Fernando, St Pourcain, Beate, Uitterlinden, Andre G., Kemp, John P., Hofman, Albert, Ring, Susan M., Cole, Tim J., Jaddoe, Vincent W.V., Smith, George Davey and Timpson, Nicholas J. (2014) Genome-wide association study of height-adjusted BMI in childhood identifies functional variant in ADCY3. Obesity, 22 10: 2252-2259. doi:10.1002/oby.20840

Author Stergiakouli, Evangelia
Gaillard, Romy
Tavare, Jeremy M.
Balthasar, Nina
Loos, Ruth J.
Taal, Hendrik R.
Evans, David M.
Rivadeneira, Fernando
St Pourcain, Beate
Uitterlinden, Andre G.
Kemp, John P.
Hofman, Albert
Ring, Susan M.
Cole, Tim J.
Jaddoe, Vincent W.V.
Smith, George Davey
Timpson, Nicholas J.
Title Genome-wide association study of height-adjusted BMI in childhood identifies functional variant in ADCY3
Journal name Obesity   Check publisher's open access policy
ISSN 1930-7381
Publication date 2014-10-01
Sub-type Article (original research)
DOI 10.1002/oby.20840
Open Access Status
Volume 22
Issue 10
Start page 2252
End page 2259
Total pages 8
Place of publication Hoboken, NJ, United States
Publisher Wiley-Blackwell Publishing
Collection year 2015
Language eng
Formatted abstract
Objective: Genome-wide association studies (GWAS) of BMI are mostly undertaken under the assumption that “kg/m2” 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.

Methods: A GWAS of height-adjusted BMI (BMI[x] = weight/heightx), 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.

Results: GWAS based on BMI[x] yielded marked differences in genomewide results profile. SNPs in ADCY3 (adenylate cyclase 3) were associated at genome-wide significance level (rs11676272 (0.28 kg/m3.1 change per allele G (0.19, 0.38), P = 6 × 10−9). In contrast, they showed marginal evidence of association with conventional BMI [rs11676272 (0.25 kg/m2 (0.15, 0.35), P = 6 × 10−7)]. Results were replicated in an independent sample, the Generation R study.

Conclusions: Analysis of BMI[x] showed differences to that of conventional BMI. The association signal at ADCY3 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.
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: Official 2015 Collection
Faculty of Medicine and Biomedical Sciences Publications
Version Filter Type
Citation counts: TR Web of Science Citation Count  Cited 14 times in Thomson Reuters Web of Science Article | Citations
Scopus Citation Count Cited 16 times in Scopus Article | Citations
Google Scholar Search Google Scholar
Created: Tue, 21 Oct 2014, 04:31:59 EST by System User on behalf of Faculty of Medicine