Assessing the influence of air pollution on cholelithiasis formation and blood lipid levels: A two-sample Mendelian randomization study

This study used a two-sample Mendelian randomization (MR) method to explore the potential causal relationship between air quality, cholelithiasis, and its related risk factor, blood lipids. This study used MR in European and East Asian groups, utilizing publicly available genome-wide association study data. The main method was inverse-variance weighting, with additional quality checks including weighted median, MR-Egger, simple, and weighted models. The Cochran Q test assessed heterogeneity. MR-Egger regression and MR-PRESSO checked for gene pleiotropy, with sensitivity tests using leave-one-out analysis. No statistically significant association was observed between air pollution and cholelithiasis in both European and East Asian populations for all pollutants analyzed, including PM2.5 (European: P = .745, East Asian: P = .209), PM2.5 to 10 (European: P = .737), PM10 (European: P = .258, East Asian: P = .977), nitrogen dioxide (European: P = .986, East Asian: P = .893), and nitrogen oxides (European: P = .902, East Asian: P = .843). However, significant correlations between air pollution and blood lipids were identified. In European populations, PM2.5 was significantly correlated with triglycerides (β = 0.428, odds ratio = 1.534, 95% confidence interval = 1.058-2.225; P = .024). In East Asian populations, PM2.5 showed a significant association with low-density lipoprotein (LDL) cholesterol (β = 0.050, odds ratio = 1.051, 95% confidence interval = 1.006-1.098; P = .026). Importantly, no evidence of heterogeneity or pleiotropy was detected in these associations, bolstering the credibility of our findings. Our study found no clear causal link between air pollution and cholelithiasis. However, we observed significant correlations between PM2.5 and triglycerides in Europeans, and between PM2.5 and LDL cholesterol in East Asians. These results suggest that PM2.5 might affect triglyceride and LDL cholesterol metabolism differently in various populations, potentially raising the risk of cholelithiasis indirectly.