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Title: Evidence for Large-Scale Gene-by-Smoking Interaction Effects on Pulmonary Function
Authors: Aschard, H.
Tobin, Martin D.
Hancock, D. B.
Skurnik, D.
Sood, A.
James, A.
Smith, A. V.
Manichaikul, A. W.
Campbell, A.
Prins1, B. P.
Hayward, C.
Loth, D. W.
Porteous, D. J.
Strachan, D. P.
Zeggini, E.
O’Connor, G.
Brusselle, G. G.
Boezen, H. M.
Schulz, H.
Deary, I. J..
Hall, I. P.
Rudan, I.
Kaprio, J.
Wilson, J. F.
Wilk, J.
Huffman, J. E.
Zhao, J. H.
de Jong, K.
Lyytikäinen, L-P.
Wain, L. V.
Jarvelin, M-R.
Kähönen, M.
Fornage, M.
Polasek, O.
Cassano, P.
Barr, R. G.
Rawal, R.
Harris, S. E.
Gharib, S. A.
Enroth, S.
Heckbert, S. R.
Lehtimäki, T.
Gyllensten, U.
Understanding Society Scientific Group
Jackson, Victoria E.
Gudnason, V.
Tang, W.
Dupuis, J.
Artigas, María Soler
Joshi, A. D.
London, S. J.
Kraft, P.
First Published: 12-Jan-2017
Publisher: Oxford University Press (OUP) for International Epidemiological Association
Citation: International Journal of Epidemiology, 2017, dyw318
Abstract: 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.
DOI Link: 10.1093/ije/dyw318
ISSN: 0300-5771
eISSN: 1464-3685
Version: Post-print
Status: Peer-reviewed
Type: Journal Article
Rights: Copyright © 2017, Oxford University Press (OUP) for International Epidemiological Association. Deposited with reference to the publisher’s open access archiving policy.
Description: The file associated with this record is under embargo until 12 months after publication, in accordance with the publisher's self-archiving policy. The full text may be available through the publisher links provided above.
Appears in Collections:Published Articles, Dept. of Health Sciences

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