Gene-occupational exposure interactions in small airways obstruction in the UK Biobank: a cross-sectional study
File(s)
Accepted version
Accepted version
Author(s)
Type
Journal Article
Abstract
Objectives: Small airways obstruction (SAO) has been associated with lifetime exposure to several agents in the workplace. Whether this association is modified by genetic variants is unknown.
Methods: Using data from 147,317 adults (33,552 with SAO; 108,762 without SAO) participating in the UK Biobank, we conducted a genome-wide association analysis to identify genetic variants associated with SAO at baseline, defined as the forced expiratory volume in 3 seconds to 6 seconds ratio (FEV3/FEV6) below the lower limit of normal. We assigned occupational exposures using the ALOHA+ job exposure matrix. Using cross-sectional data from 38,911 participants (8,363 with SAO; 30,548 without SAO), who had complete job histories, we assessed whether the identified genetic variants interacted with occupational exposure on SAO using logistic regression models adjusted for confounders. Additionally, we investigated whether gene-occupational exposure signals were associated with gene expression in lung tissue.
Results: We identified 36 genetic variants significantly associated with SAO. Eight of these significantly modified the association of SAO with pesticides, vapour, gases, dusts, fumes (VGDF), and metals, with participants homozygous for the reference allele being at increased risk of SAO when exposed to these agents. Only two of these genetic variants (rs9273529 and rs644045) appeared to affect gene expression in lung tissue. We found no significant interactions with solvents.
Conclusions: Using a large population-based cohort, we identified genetic variants that interact and modify the association between SAO and several common workplace exposures. Further research is needed to confirm these effect modifications results and clarify potential biological mechanisms.
Methods: Using data from 147,317 adults (33,552 with SAO; 108,762 without SAO) participating in the UK Biobank, we conducted a genome-wide association analysis to identify genetic variants associated with SAO at baseline, defined as the forced expiratory volume in 3 seconds to 6 seconds ratio (FEV3/FEV6) below the lower limit of normal. We assigned occupational exposures using the ALOHA+ job exposure matrix. Using cross-sectional data from 38,911 participants (8,363 with SAO; 30,548 without SAO), who had complete job histories, we assessed whether the identified genetic variants interacted with occupational exposure on SAO using logistic regression models adjusted for confounders. Additionally, we investigated whether gene-occupational exposure signals were associated with gene expression in lung tissue.
Results: We identified 36 genetic variants significantly associated with SAO. Eight of these significantly modified the association of SAO with pesticides, vapour, gases, dusts, fumes (VGDF), and metals, with participants homozygous for the reference allele being at increased risk of SAO when exposed to these agents. Only two of these genetic variants (rs9273529 and rs644045) appeared to affect gene expression in lung tissue. We found no significant interactions with solvents.
Conclusions: Using a large population-based cohort, we identified genetic variants that interact and modify the association between SAO and several common workplace exposures. Further research is needed to confirm these effect modifications results and clarify potential biological mechanisms.
Date Issued
2025-09-01
Date Acceptance
2025-09-29
Citation
Occupational and Environmental Medicine, 2025, 82 (9), pp.444-450
ISSN
1351-0711
Publisher
BMJ Publishing Group
Start Page
444
End Page
450
Journal / Book Title
Occupational and Environmental Medicine
Volume
82
Issue
9
Copyright Statement
Copyright © Author(s) (or their employer(s)) 2025. This is the author’s accepted manuscript made available under a CC-BY licence in accordance with Imperial’s Research Publications Open Access policy (www.imperial.ac.uk/oa-policy)
License URL
Publication Status
Published
Date Publish Online
2025-10-13