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

Publication type

Journal Article

Authors

Publication date

June 15, 2017

Summary:

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.

Published in

International Journal of Epidemiology

Volume and page numbers

Volume: 46 , p.894 -904

DOI

http://dx.doi.org/10.1093/ije/dyw318

ISSN

3005771

Subjects

Notes

Open Access

This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited.

© The Author 2017. Published by Oxford University Press on behalf of the International Epidemiological Association

#524010

News

Latest findings, new research

Publications search

Search all research by subject and author

Podcasts

Researchers discuss their findings and what they mean for society

Projects

Background and context, methods and data, aims and outputs

Events

Conferences, seminars and workshops

Survey methodology

Specialist research, practice and study

Taking the long view

ISER's annual report

Themes

Key research themes and areas of interest