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
Serval ID
serval:BIB_667DF213E3E1
Type
Article: article from journal or magazin.
Collection
Publications
Title
Stratification by smoking status reveals an association of CHRNA5-A3-B4 genotype with body mass index in never smokers.
Journal
PLoS Genetics
Author(s)
Taylor A.E., Morris R.W., Fluharty M.E., Bjorngaard J.H., Åsvold B.O., Gabrielsen M.E., Campbell A., Marioni R., Kumari M., Hällfors J., Männistö S., Marques-Vidal P., Kaakinen M., Cavadino A., Postmus I., Husemoen L.L., Skaaby T., Ahluwalia T.S., Treur J.L., Willemsen G., Dale C., Wannamethee S.G., Lahti J., Palotie A., Räikkönen K., Kisialiou A., McConnachie A., Padmanabhan S., Wong A., Dalgård C., Paternoster L., Ben-Shlomo Y., Tyrrell J., Horwood J., Fergusson D.M., Kennedy M.A., Frayling T., Nohr E.A., Christiansen L., Ohm Kyvik K., Kuh D., Watt G., Eriksson J., Whincup P.H., Vink J.M., Boomsma D.I., Davey Smith G., Lawlor D., Linneberg A., Ford I., Jukema J.W., Power C., Hyppönen E., Jarvelin M.R., Preisig M., Borodulin K., Kaprio J., Kivimaki M., Smith B.H., Hayward C., Romundstad P.R., Sørensen T.I., Munafò M.R., Sattar N.
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 21:26
Last modification date
20/08/2019 15:22
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