Genetic risk modifies the effect of long-term fine particulate matter exposure on coronary artery disease

Background: Although both environmental and genetic factors were linked to coronary artery disease (CAD), the extent to which the association of air pollution exposure with CAD can be influenced by genetic risk was not well understood. Methods: A total of 41,149 participants recruited from the project of Prediction for Atherosclerotic Cardiovascular Disease Risk in China (China-PAR) were included. Genetic risk scores of CAD were constructed based on 540 genetic variants. Long-term PM exposures were assessed by adopting satellite-based PM estimations at 1-km resolution. We used stratified Cox proportional hazards regression model to examine the impact of PM exposure and genetic risk on CAD risk, and further analyzed modification effect of genetic predisposition on association between PM exposure and CAD risk. Results: During a median of 13.01 years of follow-up, 1,373 incident CAD events were observed. Long-term PM exposure significantly increased CAD risk, and the hazard ratios (HRs) [95% confidence intervals (CIs)] were 1.27 (1.05–1.54) and 1.95 (1.57–2.42) among intermediate and high PM exposure groups compared to low PM exposure group. The relative risks of CAD were 40% (HR: 1.40, 95%CI: 1.18–1.66) and 133% (HR: 2.33, 95%CI: 1.94–2.79) higher among individuals at intermediate and high genetic risk than those at low genetic risk. Compared with individuals with both low genetic risk and low PM exposure, those with high genetic risk and high PM exposure had highest CAD risk, with HR of 4.37 (95%CI: 3.13–6.11). We observed significant multiplicative (P < 0.001) and additive interaction [relative excess risk due to interaction (95%CI): 2.75 (1.32–4.20); attributable proportion due to interaction (95%CI): 0.56 (0.42–0.70)] between genetic risk and PM exposure on CAD. Conclusion: This study provided evidence that long-term PM exposure might increase CAD risk, especially among people at high genetic risk. Our findings highlighted the importance of taking strategies on air quality improvement to cardiovascular disease prevention.