Please use this identifier to cite or link to this item:
https://hdl.handle.net/2440/98857
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Type: | Journal article |
Title: | Stratification by smoking status reveals an association of CHRNA5-A3-B4 genotype with Body Mass Index in never smokers |
Author: | Taylor, A. Morris, R. Fluharty, M. Bjorngaard, J. Åsvold, B. Gabrielsen, M. Campbell, A. Marioni, R. Kumari, M. Hällfors, J. Männistö, S. Marques-Vidal, P. Kaakinen, M. Cavadino, A. Postmus, I. Husemoen, L. Skaaby, T. Ahluwalia, T. Treur, J. Willemsen, G. et al. |
Citation: | PLoS Genetics, 2014; 10(12):e1004799-1-e1004799-6 |
Publisher: | Public Library of Science |
Issue Date: | 2014 |
ISSN: | 1553-7390 1553-7404 |
Editor: | Gibson, G. |
Statement of Responsibility: | Amy E. Taylor ... Debbie Lawlor ... et al. |
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. |
Keywords: | Receptors, Nicotinic Nerve Tissue Proteins Body Mass Index |
Rights: | © 2014 Taylor et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. |
DOI: | 10.1371/journal.pgen.1004799 |
Published version: | http://dx.doi.org/10.1371/journal.pgen.1004799 |
Appears in Collections: | Aurora harvest 7 Medicine publications |
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hdl_98857.pdf | Published version | 279.13 kB | Adobe PDF | View/Open |
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