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

Aschard, Hugues; Tobin, Martin D.; Hancock, Dana B.; Skurnik, David; Sood, Akshay; James, Alan; Vernon Smith, Albert; Manichaikul, Ani W.; Campbell, Archie; Prins, Bram P.; Hayward, Caroline; Loth, Daan W.; Porteous, David J.; Strachan, David P.; Zeggini, Eleftheria; O�Connor, George T.; Brusselle, Guy G.; Boezen, H. Marike; Schulz, Holger; Deary, Ian J.; Hall, Ian P.; Rudan, Igor; Kaprio, Jaakko; Wilson, James F.; Wilk, Jemma B.; Huffman, Jennifer E.; Hua Zhao, Jing; de Jong, Kim; Lyytik�inen, Leo-Pekka; Wain, Louise V.; Jarvelin, Marjo-Riitta; K�h�nen, Mika; Fornage, Myriam; Polasek, Ozren; Cassano, Patricia A.; Barr, R. Graham; Rawal, Rajesh; Harris, Sarah E.; Gharib, Sina A.; Enroth, Stefan; Heckbert, Susan R.; Lehtim�ki, Terho; Gyllensten, Ulf; Gudnason, Vilmundur; Jackson, Victoria E.; Tang, Wenbo; Dupuis, Jos�e; Soler Artigas, Mar�a; Joshi, Amit D.; London, Stephanie J.; Kraft, Peter

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Authors

Hugues Aschard

Martin D. Tobin

Dana B. Hancock

David Skurnik

Akshay Sood

Alan James

Albert Vernon Smith

Ani W. Manichaikul

Archie Campbell

Bram P. Prins

Caroline Hayward

Daan W. Loth

David J. Porteous

David P. Strachan

Eleftheria Zeggini

George T. O�Connor

Guy G. Brusselle

H. Marike Boezen

Holger Schulz

Ian J. Deary

Ian P. Hall

Igor Rudan

Jaakko Kaprio

James F. Wilson

Jemma B. Wilk

Jennifer E. Huffman

Jing Hua Zhao

Kim de Jong

Leo-Pekka Lyytik�inen

Louise V. Wain

Marjo-Riitta Jarvelin

Mika K�h�nen

Myriam Fornage

Ozren Polasek

Patricia A. Cassano

R. Graham Barr

Rajesh Rawal

Sarah E. Harris

Sina A. Gharib

Stefan Enroth

Susan R. Heckbert

Terho Lehtim�ki

Ulf Gyllensten

Vilmundur Gudnason

Victoria E. Jackson

Wenbo Tang

Jos�e Dupuis

Mar�a Soler Artigas

Amit D. Joshi

Stephanie J. London

Peter Kraft



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-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 (bint=–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.

Citation

Aschard, H., Tobin, M. D., Hancock, D. B., Skurnik, D., Sood, A., James, A., …Kraft, P. (in press). Evidence for large-scale gene-by-smoking interaction effects on pulmonary function. International Journal of Epidemiology, Article dyw318. https://doi.org/10.1093/ije/dyw318

Journal Article Type Article
Acceptance Date Oct 10, 2016
Online Publication Date Jan 12, 2017
Deposit Date Jul 21, 2017
Publicly Available Date Jul 21, 2017
Journal International Journal of Epidemiology
Print ISSN 0300-5771
Electronic ISSN 1464-3685
Publisher Oxford University Press
Peer Reviewed Peer Reviewed
Article Number dyw318
DOI https://doi.org/10.1093/ije/dyw318
Public URL https://nottingham-repository.worktribe.com/output/840601
Publisher URL https://academic.oup.com/ije/article-lookup/doi/10.1093/ije/dyw318
Contract Date Jul 21, 2017

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