Exploring the genetic effects of exposure to hazardous workplaces on the risk of respiratory disease by two-sample mendelian randomization and bioinformatics analysis

Background Harsh workplace can include very cold, hot, and dusty workplaces, as well as exposure in the workplace with chemicals and other fumes, cigarette smoke, and diesel exhaust. There is a shortage of genetic evidence regarding the impact of harsh workplaces on respiratory health. Objective This study aims to investigate the genetic association between harsh workplace and respiratory diseases. Methods This study used two-sample Mendelian randomization analysis based on UK Biobank, FinnGen Project, and IEU Open GWAS Database to exclude confounding factors and investigate the association between workplace and respiratory diseases. Results Frequent exposure to workplace with cigarette smoke increased the risk of allergic rhinitis (β IVW = 1.83, P = 0.022). Intermittent exposure to extremely cold workplaces exacerbated asthma (β IVW = 0.34, P = 0.011) and COPD (β IVW = 0.80, P = 0.002). Rare (β MR = 1.15, P = 0.037) or intermittent exposure (β IVW = 0.59, P = 0.019) to extremely hot workplaces may worsen COPD. Chemical/smoke exposure may aggravate emphysema (β IVW = 0.03, P = 0.016). Exposure to extremely hot (β IVW = 0.90, P = 0.016) and dusty workplaces (β IVW = 0.97, P = 0.005) increased lung cancer risk. Exposure to extremely cold workplaces was associated with pneumoconiosis (β IVW = 3.99, P = 0.028) and was a significant risk factor for IPF (β IVW = 3.28, P = 0.015). Rare (β IVW = 1.69, P = 0.011) or frequent exposure (β IVW = 1.44, P = 0.013) to dusty workplaces increased tuberculosis risk. Conclusions Our study excluded other confounding factors and revealed a causal relationship between harsh workplaces and respiratory disease from genetic inheritance. Incorporating genetic evidence into occupational health assessments helps accurately identify high-risk individuals, develop personalized intervention plans, and enhance the effectiveness of respiratory health protection for workers.