Stratification by smoking status reveals an association of CHRNA5-A3-B4 genotype with body mass index in never smokers.

A.E. Taylor; R.W. Morris; M.E. Fluharty; J.H. Bjorngaard; B.O. Åsvold; M.E. Gabrielsen; A. Campbell; R. Marioni; M. Kumari; J. Hällfors; S. Männistö; P. Marques-Vidal; M. Kaakinen; A. Cavadino; I. Postmus; L.L. Husemoen; T. Skaaby; T.S. Ahluwalia; J.L. Treur; G. Willemsen; C. Dale; S.G. Wannamethee; J. Lahti; A. Palotie; K. Räikkönen; A. Kisialiou; A. McConnachie; S. Padmanabhan; A. Wong; C. Dalgård; L. Paternoster; Y. Ben-Shlomo; J. Tyrrell; J. Horwood; D.M. Fergusson; M.A. Kennedy; T. Frayling; E.A. Nohr; L. Christiansen; K. Ohm Kyvik; D. Kuh; G. Watt; J. Eriksson; P.H. Whincup; J.M. Vink; D.I. Boomsma; G. Davey Smith; D. Lawlor; A. Linneberg; I. Ford; J.W. Jukema; C. Power; E. Hyppönen; M.R. Jarvelin; M. Preisig; K. Borodulin; J. Kaprio; M. Kivimaki; B.H. Smith; C. Hayward; P.R. Romundstad; T.I. Sørensen; M.R. Munafò; N. Sattar

Stratification by smoking status reveals an association of CHRNA5-A3-B4 genotype with body mass index in never smokers.

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2014

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Anglais

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doi: 10.1371/journal.pgen.1004799
issn: 1553-7390

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Serveur académique Lausannois

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Ce document est lié à :
info:eu-repo/semantics/altIdentifier/doi/10.1371/journal.pgen.1004799

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info:eu-repo/semantics/altIdentifier/pmid/25474695

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info:eu-repo/semantics/altIdentifier/eissn/1553-7404

Ce document est lié à :
info:eu-repo/semantics/altIdentifier/urn/urn:nbn:ch:serval-BIB_667DF213E3E16

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Serveur Académique Lausannois

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Université de Lausanne et CHUV

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info:eu-repo/semantics/openAccess , Copying allowed only for non-profit organizations , https://serval.unil.ch/disclaimer

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Tobacco smoking Cigarette habit Cigarette smoking

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A.E. Taylor et al., « Stratification by smoking status reveals an association of CHRNA5-A3-B4 genotype with body mass index in never smokers. », Serveur académique Lausannois, ID : 10.1371/journal.pgen.1004799

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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.

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Stratification by smoking status reveals an association of CHRNA5-A3-B4 genotype with body mass index in never smokers.

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