Publication type
Journal Article
Authors
- Amy E. Taylor
- Richard W. Morris
- Meg E. Fluharty
- Johan H. Bjørngaard
- Bjørn Olav Åsvold
- Maiken E. Gabrielsen
- Archie Campbell
- Riccardo Marioni
- Meena Kumari
- Jenni Hällfors
- Satu Männistö
- Pedro Marques-Vidal
- Marika Kaakinen
- Alana Cavadino
- Iris Postmus
- Lise Lotte N. Husemoen
- Tea Skaaby
- Tarunveer S. Ahluwalia
- Jorien L. Treur
- Gonneke Willemsen
- Caroline Dale
- S. Goya Wannamethee
- Jari Lahti
- Aarno Palotie
- Katri Räikkönen
- Aliaksei Kisialiou
- Alex McConnachie
- Sandosh Padmanabhan
- Andrew Wong
- Christine Dalgård
- Lavinia Paternoster
- Yoav Ben-Shlomo
- Jessica Tyrrell
- John Horwood
- David M. Fergusson
- Martin A. Kennedy
- Tim Frayling
- Ellen A. Nohr
- Lene Christiansen
- Kirsten Ohm Kyvik
- Diana Kuh
- Graham Watt
- Johan Eriksson
- Peter H. Whincup
- Jacqueline M. Vink
- Dorret I. Boomsma
- George Davey Smith
- Debbie Lawlor
- Allan Linneberg
- Ian Ford
- J. Wouter Jukema
- Christine Power
- Elina Hyppönen
- Marjo-Riitta Jarvelin
- Martin Preisig
- Katja Borodulin
- Jaakko Kaprio
- Mika Kivimaki
- Blair H. Smith
- Caroline Hayward
- Pål R. Romundstad
- Thorkild I. A. Sørensen
- Marcus R. Munafò
- Naveed Sattar
Publication date
December 15, 2014
Summary:
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 = 2.00610210), but also unexpectedly found that it was associated
with 0.35% higher BMI in never smokers (95% CI +0.18 to +0.52, P = 6.3861025).
An interaction test confirmed that these estimates differed from each other (P
= 4.95610213). 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.
Published in
PLoS Genetics
Volume
Volume: 10
DOI
http://dx.doi.org/10.1371/journal.pgen.1004799
ISSN
15537390
Subjects
Notes
OpenAccess article
Copyright: © 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.
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