Genetic Susceptibility Modifies Relationships Between Air Pollutants and Stroke Risk: A Large Cohort Study

Abstract

BACKGROUND: The extent to which genetic susceptibility modifies the associations between air pollutants and the risk of incident stroke is still unclear. This study was designed to investigate the separate and joint associations of long-term exposure to air pollutants and genetic susceptibility on stroke risk. METHODS: The participants of this study were recruited by the UK Biobank between 2006 and 2010. These participants were followed up from the enrollment until the occurrence of stroke events or censoring of data. Hazard ratios (HRs) and 95% CIs for stroke events associated with long-term exposure to air pollutants were estimated by fitting both crude and adjusted Cox proportional hazards models. Additionally, the polygenic risk score was calculated to estimate whether the polygenic risk score modifies the associations between exposure to air pollutants and incident stroke. RESULTS: A total of 502 480 subjects were included in this study. After exclusion, 452 196 participants were taken into the final analysis. During a median follow-up time of 11.7 years, 11 334 stroke events were observed, with a mean age of 61.60 years, and men accounted for 56.2% of the total cases. Long-term exposures to particulate matter with an aerodynamic diameter smaller than 2.5 µm (adjusted HR, 1.70 [95% CI, 1.43–2.03]) or particulate matter with an aerodynamic diameter smaller than 10 µm (adjusted HR, 1.50 [95% CI, 1.36–1.66]), nitrogen dioxide (adjusted HR, 1.10 [95% CI, 1.07–1.12]), and nitrogen oxide (adjusted HR, 1.04 [95% CI, 1.02–1.05]) were pronouncedly associated with increased risk of stroke. Meanwhile, participants with high genetic risk and exposure to high air pollutants had ≈45% (31%, 61%; particulate matter with an aerodynamic diameter smaller than 2.5 µm), 48% (33%, 65%; particulate matter with an aerodynamic diameter smaller than 10 µm), 51% (35%, 69%; nitrogen dioxide), and 39% (25%, 55%; nitrogen oxide) higher risk of stroke compared with those with low genetic risk and exposure to low air pollutants, respectively. Of note, we observed additive and multiplicative interactions between genetic susceptibility and air pollutants on stroke events. CONCLUSIONS: Chronic exposure to air pollutants was associated with an increased risk of stroke, especially in populations at high genetic risk.