Hugues Aschard
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
Authors
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 |
Files
dyw318.pdf
(617 Kb)
PDF
Copyright Statement
Copyright information regarding this work can be found at the following address: http://eprints.nottingham.ac.uk/end_user_agreement.pdf
You might also like
Genome-wide association study to identify genetic determinants of severe asthma
(2012)
Journal Article
Downloadable Citations
About Repository@Nottingham
Administrator e-mail: discovery-access-systems@nottingham.ac.uk
This application uses the following open-source libraries:
SheetJS Community Edition
Apache License Version 2.0 (http://www.apache.org/licenses/)
PDF.js
Apache License Version 2.0 (http://www.apache.org/licenses/)
Font Awesome
SIL OFL 1.1 (http://scripts.sil.org/OFL)
MIT License (http://opensource.org/licenses/mit-license.html)
CC BY 3.0 ( http://creativecommons.org/licenses/by/3.0/)
Powered by Worktribe © 2024
Advanced Search