Genetic Susceptibility to Impaired Lung Function in Underground Coal Miners from Kazakhstan

Occupational exposure to coal mine dust is a major risk factor for respiratory impairment; however, the genetic determinants of individual variation in lung function remain poorly understood, particularly in occupational cohorts that have been largely absent from genome-wide association studies. This study aimed to identify genetic variants associated with quantitative lung function traits in underground coal miners from Kazakhstan.

A total of 186 underground coal miners from the Karaganda coal basin were genotyped using the Illumina Global Screening Array. Genome-wide association analyses were performed for six spirometric parameters (FVC, FEV1, FEV1/FVC, MEF25, MEF50, and MEF75), adjusting for age, mining exposure, body mass index, smoking status, and population structure. Genotype imputation was performed to increase genomic coverage and evaluate the consistency of association signals.

No variants reached the conventional genome-wide significance threshold. However, recurrent suggestive associations identified PRKCB, FANCE, and UBTD1 as the principal candidate loci across correlated spirometric parameters, with independent support from genotype imputation.

Recurrent associations across complementary spirometric parameters identified biologically plausible candidate loci involved in inflammatory signalling, DNA repair, and epithelial homeostasis. These findings provide one of the first genomic insights into lung function in underground coal miners and provide a foundation for future validation and functional studies.