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Genome-wide association study of height-adjusted BMI in childhood identifies functional variant in ADCY3
OBJECTIVE: Genome-wide association studies (GWAS) of BMI are mostly undertaken under the assumption that “kg/m(2)” 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 p...
Autores principales: | , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
BlackWell Publishing Ltd
2014
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4265207/ https://www.ncbi.nlm.nih.gov/pubmed/25044758 http://dx.doi.org/10.1002/oby.20840 |
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author | 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 WV Davey Smith, George Timpson, Nicholas J |
author_facet | 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 WV Davey Smith, George Timpson, Nicholas J |
author_sort | Stergiakouli, Evangelia |
collection | PubMed |
description | OBJECTIVE: Genome-wide association studies (GWAS) of BMI are mostly undertaken under the assumption that “kg/m(2)” 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/height(x)), 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/m(3.1) 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/m(2) (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. |
format | Online Article Text |
id | pubmed-4265207 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2014 |
publisher | BlackWell Publishing Ltd |
record_format | MEDLINE/PubMed |
spelling | pubmed-42652072014-12-19 Genome-wide association study of height-adjusted BMI in childhood identifies functional variant in ADCY3 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 WV Davey Smith, George Timpson, Nicholas J Obesity (Silver Spring) Original Articles OBJECTIVE: Genome-wide association studies (GWAS) of BMI are mostly undertaken under the assumption that “kg/m(2)” 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/height(x)), 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/m(3.1) 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/m(2) (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. BlackWell Publishing Ltd 2014-10 2014-07-21 /pmc/articles/PMC4265207/ /pubmed/25044758 http://dx.doi.org/10.1002/oby.20840 Text en Copyright © 2014 The Obesity Society http://creativecommons.org/licenses/by/3.0/ This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Original Articles 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 WV Davey Smith, George Timpson, Nicholas J Genome-wide association study of height-adjusted BMI in childhood identifies functional variant in ADCY3 |
title | Genome-wide association study of height-adjusted BMI in childhood identifies functional variant in ADCY3 |
title_full | Genome-wide association study of height-adjusted BMI in childhood identifies functional variant in ADCY3 |
title_fullStr | Genome-wide association study of height-adjusted BMI in childhood identifies functional variant in ADCY3 |
title_full_unstemmed | Genome-wide association study of height-adjusted BMI in childhood identifies functional variant in ADCY3 |
title_short | Genome-wide association study of height-adjusted BMI in childhood identifies functional variant in ADCY3 |
title_sort | genome-wide association study of height-adjusted bmi in childhood identifies functional variant in adcy3 |
topic | Original Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4265207/ https://www.ncbi.nlm.nih.gov/pubmed/25044758 http://dx.doi.org/10.1002/oby.20840 |
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