8216436 Interaction between occupational exposures and genetic variants on small airways obstruction

<h3>Objective</h3> Small airways obstruction (SAO) is a common condition in adults that precedes chronic obstructive pulmonary disease, a leading global cause of morbidity and mortality. SAO has been associated with different occupational exposures, but it is unclear if a genetic predisposition increases the effect of these occupational exposures on SAO. <h3>Methods</h3> We used data from 147,317 adults (33,552 SAO cases, 108,762 controls) participating in the UK Biobank national cohort. Occupational exposures were assigned to each participant using the ALOHA+ job exposure matrix (pesticides, solvents, metals and vapour, gases, dust and fumes). SAO was defined as the forced expiratory volume in three seconds to six seconds ratio (FEV3/FEV6) below the lower limit of normal. To identify genetic variants associated with SAO, we first conducted a genome-wide association analysis. We then analysed the interaction between the identified genetic variants and occupational exposure on SAO using logistic regression models adjusted for confounders. Additionally, we explored if the identified gene-occupational exposure signals were associated with gene expression in lung tissue. <h3>Results</h3> A total of 36 genetic variants were significantly associated with SAO. Of these, eight variants modified the relationship between SAO and exposure to all vapours, gases, dusts, fumes (VGDF), pesticides and metals. Homozygotes for the effect allele showed an increased risk of SAO when exposed to these agents. Only two of these variants (rs9273529 in HLA-DQB1 and rs644045 in C2) showed a moderate influence on gene expression in lung tissue. <h3>Conclusion</h3> In this large population-based cohort, we identified 8 out of 36 genetic variants interacting with common occupational exposures to modify the risk of SAO. Further research is required to validate these findings and better understand potential biological mechanisms involved.