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

Aschard, H; Tobin, MD; Hancock, DB; Skurnik, D; Sood, A; James, A; Vernon Smith, A; Manichaikul, AW; Campbell, A; Prins, BP; et al. Aschard, H; Tobin, MD; Hancock, DB; Skurnik, D; Sood, A; James, A; Vernon Smith, A; Manichaikul, AW; Campbell, A; Prins, BP; Hayward, C; Loth, DW; Porteous, DJ; Strachan, DP; Zeggini, E; O'Connor, GT; Brusselle, GG; Boezen, HM; Schulz, H; Deary, IJ; Hall, IP; Rudan, I; Kaprio, J; Wilson, JF; Wilk, JB; Huffman, JE; Hua Zhao, J; de Jong, K; Lyytikäinen, L-P; Wain, LV; Jarvelin, M-R; Kähönen, M; Fornage, M; Polasek, O; Cassano, PA; Barr, RG; Rawal, R; Harris, SE; Gharib, SA; Enroth, S; Heckbert, SR; Lehtimäki, T; Gyllensten, U; Society Scientific Group, U; Jackson, VE; Gudnason, V; Tang, W; Dupuis, J; Soler Artigas, M; Joshi, AD; London, SJ; Kraft, P (2017) Evidence for large-scale gene-by-smoking interaction effects on pulmonary function. Int J Epidemiol, 46 (3). pp. 894-904. ISSN 1464-3685 https://doi.org/10.1093/ije/dyw318
SGUL Authors: Strachan, David Peter

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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 (βint = -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 FEV 1: /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.

Item Type: Article
Additional Information: © The Author 2017. Published by Oxford University Press on behalf of the International Epidemiological Association 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.
Keywords: FEV1/FVC, genetic risk score, gene–environment interaction, smoking, FEV1/FVC, smoking, gene-environment interaction, genetic risk score, Epidemiology, 0104 Statistics, 1117 Public Health And Health Services
SGUL Research Institute / Research Centre: Academic Structure > Population Health Research Institute (INPH)
Journal or Publication Title: Int J Epidemiol
ISSN: 1464-3685
Language: eng
Dates:
DateEvent
June 2017Published
12 January 2017Published Online
10 October 2016Accepted
Publisher License: Creative Commons: Attribution 4.0
Projects:
Project IDFunderFunder ID
R01 HL077612NHLBI NIH HHSUNSPECIFIED
MR/K026992/1Medical Research Councilhttp://dx.doi.org/10.13039/501100000265
R01 HL093081NHLBI NIH HHSUNSPECIFIED
CZD/16/6/4Chief Scientist Officehttp://dx.doi.org/10.13039/501100000589
MC_PC_U127561128Medical Research Councilhttp://dx.doi.org/10.13039/501100000265
G0902313Medical Research Councilhttp://dx.doi.org/10.13039/501100000265
BB/F019394/1Biotechnology and Biological Sciences Research Councilhttp://dx.doi.org/10.13039/501100000268
G000093Medical Research Councilhttp://dx.doi.org/10.13039/501100000265
068545/Z/02Wellcome Trusthttp://dx.doi.org/10.13039/100004440
076113/B/04/ZWellcome Trusthttp://dx.doi.org/10.13039/100004440
079895Wellcome Trusthttp://dx.doi.org/10.13039/100004440
G0500539Medical Research Councilhttp://dx.doi.org/10.13039/501100000265
G0600705Medical Research Councilhttp://dx.doi.org/10.13039/501100000265
G1002319Medical Research Councilhttp://dx.doi.org/10.13039/501100000265
PrevMetSyn/SALVEMedical Research Councilhttp://dx.doi.org/10.13039/501100000265
PubMed ID: 28082375
Web of Science ID: WOS:000406242600023
Go to PubMed abstract
URI: http://openaccess.sgul.ac.uk/id/eprint/108393
Publisher's version: https://doi.org/10.1093/ije/dyw318

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