Genetic insights into the causal relationship between air pollutants and atrial fibrillation: a Mendelian randomization study.

Abstract

Previous observational studies reported associations between air pollutants and atrial fibrillation (AF), but their causal relationships remain unclear. We conducted a two-sample Mendelian randomization (MR) analysis using genome-wide association studies (GWAS) summary data from the UK Biobank and IEU Open GWAS databases to investigate the genetic causality between air pollutants and AF. Air pollutants were subdivided into nitrogen dioxide (NO₂) and particulate matter (PM_2.5 and PM₁₀), with single-nucleotide polymorphisms (SNPs) associated with each pollutant identified as instrumental variables (IVs). Subsequently, MR methods including MR-Egger, weighted median, inverse variance weighted (IVW), simple mode, and weighted mode were applied to assess genetic causality, while pleiotropy, heterogeneity, and reliability were also evaluated. IVW findings indicate a consequential correlation between NO₂ and increased AF risk, as evidenced by an odds ratio (OR 1.948 [95% confidence interval [CI] 1.011-3.756]; p = 0.046). Conversely, the causal effect of PM_2.5 (OR 1.274 [95% CI 0.651-2.493; p = 0.480) and PM₁₀ (OR 1.162 [95% CI 0.891-1.517]; p = 0.268) with AF was not statistically significant. The analysis revealed the absence of pleiotropy (p > 0.05). However, PM_2.5 displayed significant heterogeneity (p = 0.2385), whereas NO₂ (p = 0.5365) and PM₁₀ (p = 0.7789) did not. This MR analysis suggested a causal effect of NO₂ on AF, but not for PM_2.5 or PM₁₀.