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Aschard, H.* ; Tobin, M.D.* ; Hancock, D.B.* ; Skurnik, D.* ; Sood, A.* ; James, A.* ; Smith, A.V.* ; Manichaikul, A.* ; Campbell, A.* ; Prins, B.P.* ; Hayward, C.* ; Loth, D.W.* ; Porteous, D.J.* ; Strachan, D.P.* ; Zeggini, E.* ; O'Connor, G.T.* ; Brusselle, G.G.* ; Boezen, H.M.* ; Schulz, H. ; Deary, I.J.* ; Hall, I.P.* ; Rudan, I.* ; Kaprio, J.* ; Wilson, J.F.* ; Wilk, J.B.* ; 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.A.* ; Barr, R.G.* ; Rawal, R. ; Harris, S.E.* ; Gharib, S.A.* ; Enroth, S.* ; Heckbert, S.R.* ; Lehtimäki, T.* ; Gyllensten, U.* ; Jackson, V.E.* ; Gudnason, V.* ; Tang, W.* ; Dupuis, J.* ; Artigas, M.S.* ; Joshi, A.D.* ; London, S.J.* ; Kraft, P.*

Evidence for large-scale gene-by-smoking interaction effects on pulmonary function.

Int. J. Epidemiol. 46, 894-904 (2017)
Publ. Version/Full Text Research data DOI PMC
Open Access Gold (Paid Option)
Creative Commons Lizenzvertrag
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-single nucleotide polymorphisms (SNPs) genetic risk score in relation to FEV1 or FEV1/FVC in 50 047 participants of European ancestry from the Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) and SpiroMeta consortia. Results: We identified an interaction (beta(int) = -0.036, 95% confidence interval, -0.040 to -0.032, P = 0.00057) between an unweighted 26 SNP 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. A replication analysis in two independent datasets, although not statistically significant, showed a similar trend in the interaction effect. 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.
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Publication type Article: Journal article
Document type Scientific Article
Corresponding Author
Keywords Fev1/fvc ; Smoking ; Gene-environment Interaction ; Genetic Risk Score; Genome-wide Association; Environment Interactions; Lung-function; Risk; Epidemiology; Opportunities; Obstruction; Prediction; Fev1/fvc; Disease
ISSN (print) / ISBN 0300-5771
e-ISSN 1464-3685
Journal International Journal of Epidemiology
Quellenangaben Volume: 46, Issue: 3, Pages: 894-904 Article Number: , Supplement: ,
Publisher Oxford University Press
Publishing Place Oxford
Non-patent literature Publications
Reviewing status Peer reviewed
Institute(s) Institute of Epidemiology (EPI)
Institute of Epidemiology II (EPI2)
Institute of Genetic Epidemiology (IGE)