Fine particulate matter constituents, greenness, and incident atrial fibrillation: joint effect with genetic susceptibility

AIMS: To date, limited evidence has assessed the relationships of long-term exposures to PM2.5 constituents and greenness with AF incidence. This study aimed to examine the association between these exposures and incident AF, and further assess the joint effects of genetic susceptibility. METHODS AND RESULTS: PM2.5 constituents and greenness were estimated around the residence of 411 364 UK adults. Time-varying Cox models were used to examine these associations. The polygenic risk score (PRS) assessed genetic susceptibility to AF and explore the joint effect between genes and exposures. The hazard ratios (HRs) [95% confidence intervals (CIs)] of AF for per interquartile range increase in elemental carbon (EC), organic matter (OM), ammonium (NH4+), nitrate (NO3-), sulfate (SO42-), NDVI300m, NDVI500m, NDVI1000m, and NDVI1500m were 1.05 (1.03, 1.07), 1.06 (1.04, 1.08), 1.07 (1.05, 1.10), 1.05 (1.03, 1.07), 1.06 (1.04, 1.09), 0.97 (0.95, 0.99), 0.96 (0.94, 0.98), 0.95 (0.94, 0.97), and 0.95 (0.93, 0.97), respectively. Among PM2.5 constituents, SO42- (43.8%) was the main contributor to AF in the mixture model. Mediation analyses found that negative association between greenness and AF risk was partially mediated by mitigating exposure to PM2.5 constituents. Moreover, there were additive interactions between EC, OM, NH4+, NO3-, SO42-, and NDVI1500m and PRS. Joint effect revealed that participants with a high PRS and high PM2.5 constituents or low greenness had the highest risk of incident AF, with HRs ranging from 3.14 (2.93, 3.37) to 3.26 (3.04, 3.51). CONCLUSION: Long-term exposure to PM2.5 constituents was positively associated with the incidence of AF, whereas greenness was inversely associated with it.