posted on 2016-11-10, 15:03authored byH. Aschard, Martin D. Tobin, D. B. Hancock, D. Skurnik, A. Sood, A. James, A. V. Smith, A. W. Manichaikul, A. Campbell, B. P. Prins1, C. Hayward, D. W. Loth, D. J. Porteous, D. P. Strachan, E. Zeggini, G. O’Connor, G. G. Brusselle, H. M. Boezen, H. Schulz, I. J.. Deary, I. P. Hall, I. Rudan, J. Kaprio, J. F. Wilson, J. Wilk, J. E. Huffman, J. H. Zhao, K. de Jong, L-P. Lyytikäinen, L. V. Wain, M-R. Jarvelin, M. Kähönen, M. Fornage, O. Polasek, P. Cassano, R. G. Barr, R. Rawal, S. E. Harris, S. A. Gharib, S. Enroth, S. R. Heckbert, T. Lehtimäki, U. Gyllensten, Understanding Society Scientific Group, Victoria E. Jackson, V. Gudnason, W. Tang, J. Dupuis, María Soler Artigas, A. D. Joshi, S. J. London, P. Kraft
Background: Smoking is the strongest environmental risk factor for reduced pulmonary
function. The genetic component of various pulmonary traits has also been demonstrated, and
at least 26 loci have been reproducibly associated with either FEV1 (forced expiratory volume in
1 second) or FEV1/FVC (FEV1/forced vital capacity). Although the main effects of smoking and
genetic loci are well established, the question of potential gene-by-smoking interaction effect
remains unanswered. The aim of the present study was to assess, using a genetic risk score
approach, whether the effect of these 26 loci on pulmonary function is influenced by smoking.
Methods: We evaluated the interaction between smoking exposure, considered as either ever
vs. never or pack-years, and a 26 SNPs genetic risk score in relation to FEV1 or FEV1/FVC in 50
047 participants of European ancestry from the CHARGE and SpiroMeta consortia.
Results: We identified an interaction (𝛽𝑖𝑛𝑡 = −0.036, 95% confidence interval, -0.040 – -0.032,
P=0.00057) between an unweighted 26 SNPs genetic risk score and smoking status (ever/never)
on the FEV1/FVC ratio. In interpreting this interaction, we showed that the genetic risk of falling
below the FEV1/FVC threshold used to diagnose chronic obstructive pulmonary disease is higher
among ever smokers than among never smokers.
Conclusions: This study highlights the benefit of using genetic risk scores for identifying
interactions missed when studying individual SNPs, and shows for the first time that persons
with the highest genetic risk for low FEV1/FVC may be more susceptible to the deleterious
effects of smoking.
Funding
The research undertaken by M.D.T., L.V.W. was partly funded by the National Institute for Health Research (NIHR). A full list of studies and authors source of funding source and acknowledgments is provided in the
Supplementary Data.
History
Citation
International Journal of Epidemiology, 2017, dyw318
Author affiliation
/Organisation/COLLEGE OF MEDICINE, BIOLOGICAL SCIENCES AND PSYCHOLOGY/School of Medicine/Department of Health Sciences
Version
AM (Accepted Manuscript)
Published in
International Journal of Epidemiology
Publisher
Oxford University Press (OUP) for International Epidemiological Association
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