Associations of genetic risk factors and air pollution with incident hypertension among participants in the UK Biobank study

Abstract

The purposes of this study were to quantify the association of the combination of air pollution and genetic risk factors with hypertension and explore the interactions between air pollution and genetic risk. This study included 391,366 participants of European ancestry initially free from pre-existing hypertension in the UK Biobank. Exposure to ambient air pollutants, including particulate matter (PM_2.5 PM_2.5-10, and PM₁₀), nitrogen dioxide (NO₂) and nitrogen oxides (NO_X), was estimated through land use regression modelling, and the associations between air pollutants and the incidence of hypertension were investigated using a Cox proportional hazards model adjusted for covariates. Furthermore, we established a polygenic risk score for hypertension and assessed the combined effect of genetic susceptibility and air pollution on incident hypertension. The results showed significant associations between the risk of hypertension and exposure to PM_2.5 (hazard ratio [HR]: 1.41, 95% confidence interval [CI]: 1.29-1.53; per 10 μg/m³), PM₁₀ (1.05, 1.00-1.09; per 10 μg/m³), and NO_X (1.01, 1.01-1.02 per 10 μg/m³). Additive effects of PM_2.5 and NO_X exposure and genetic risk were observed. Compared to individuals with a low genetic risk and low air pollution exposure, participants with high air pollution exposure and a high genetic risk had a significantly increased risk of hypertension (PM_2.5: 71% (66%-76%), PM₁₀: 59% (55%-64%), NO_X: 65% (60%-70%)). Our results indicate that long-term exposure to air pollution is associated with an increased risk of hypertension, especially in individuals with a high genetic risk.

Keywords: Additive interaction; Air pollution; Genetic susceptibility; Hypertension; Polygenic risk score.