Causal associations of air pollutants with chest and gingival pain: Genetic insight from Mendelian randomization study

Epidemiological studies have already established associations between air pollutants and adverse health outcomes, but the causal associations between air pollutants and chest pain (CP) and gingival pain (GP) remain unclear. This study aimed to explore the potential causal effects of air pollutants on CP and GP. Utilizing genome-wide association study summary statistics from European-ancestry populations, we conducted bidirectional two-sample Mendelian randomization (MR) analyses. Causal estimates were primarily derived through inverse-variance weighted regression, weighted median, MR-Egger, and weighted mode methods to assess pleiotropy and robustness. Multivariable MR (MVMR) further adjusted for smoking and alcohol consumption covariates. MR analyses demonstrated significant causal effects of particulate matter (PM) 2.5 exposure on both CP (OR = 1.060, 95% CI: 1.036–1.085, P = 5.51 × 10 −07 ) and GP (OR = 1.031, 95% CI: 1.008–1.056, P = .008). Further MVMR analysis supported that the causal associations of PM 2.5 exposure with CP and GP persisted after controlling for smoking and alcohol consumption. No significant causal effects were observed for PM10, PM2.5-10, or nitrogen oxides exposure. Our findings provide novel genetic evidence that long-term PM₂.₅ exposure independently increases risks of CP and GP, underscoring the need for targeted air quality interventions and public health strategies to mitigate particulate matter-related disease burden.