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.