Stratification by smoking status reveals an association of CHRNA5-A3-B4 genotype with body mass index in never smokers.
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Version: author
State: Public
Version: author
Serval ID
serval:BIB_667DF213E3E1
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Stratification by smoking status reveals an association of CHRNA5-A3-B4 genotype with body mass index in never smokers.
Journal
PLoS Genetics
ISSN
1553-7404 (Electronic)
ISSN-L
1553-7390
Publication state
Published
Issued date
2014
Volume
10
Number
12
Pages
e1004799
Language
english
Notes
Publication types: Journal Article ; Research Support, Non-U.S. Gov'tPublication Status: epublish
Abstract
We previously used a single nucleotide polymorphism (SNP) in the CHRNA5-A3-B4 gene cluster associated with heaviness of smoking within smokers to confirm the causal effect of smoking in reducing body mass index (BMI) in a Mendelian randomisation analysis. While seeking to extend these findings in a larger sample we found that this SNP is associated with 0.74% lower body mass index (BMI) per minor allele in current smokers (95% CI -0.97 to -0.51, P = 2.00 × 10(-10)), but also unexpectedly found that it was associated with 0.35% higher BMI in never smokers (95% CI +0.18 to +0.52, P = 6.38 × 10(-5)). An interaction test confirmed that these estimates differed from each other (P = 4.95 × 10(-13)). This difference in effects suggests the variant influences BMI both via pathways unrelated to smoking, and via the weight-reducing effects of smoking. It would therefore be essentially undetectable in an unstratified genome-wide association study of BMI, given the opposite association with BMI in never and current smokers. This demonstrates that novel associations may be obscured by hidden population sub-structure. Stratification on well-characterized environmental factors known to impact on health outcomes may therefore reveal novel genetic associations.
Pubmed
Web of science
Open Access
Yes
Create date
29/01/2015 20:26
Last modification date
20/08/2019 14:22