Mendelian randomization study supports the causal effects of air pollution on longevity via multiple age-related diseases.

Growing evidence suggests that exposure to fine particulate matter (PM_2.5) may reduce life expectancy; however, the causal pathways of PM_2.5 exposure affecting life expectancy remain unknown. Here, we assess the causal effects of genetically predicted PM_2.5 concentration on common chronic diseases and longevity using a Mendelian randomization (MR) statistical framework based on large-scale genome-wide association studies (GWAS) (>400,000 participants). After adjusting for other types of air pollution and smoking, we find significant causal relationships between PM_2.5 concentration and angina pectoris, hypercholesterolaemia and hypothyroidism, but no causal relationship with longevity. Mediation analysis shows that although the association between PM_2.5 concentration and longevity is not significant, PM_2.5 exposure indirectly affects longevity via diastolic blood pressure (DBP), hypertension, angina pectoris, hypercholesterolaemia and Alzheimer's disease, with a mediated proportion of 31.5, 70.9, 2.5, 100, and 24.7%, respectively. Our findings indicate that public health policies to control air pollution may help improve life expectancy.