To assess whether there are causal associations between four air pollutants [nitrogen dioxide (NO₂), nitrogen oxides (NO_x), fine particulate matter (PM_2.5), and inhalable particulate matter (PM₁₀)] and the risk of ischemic stroke, intracerebral hemorrhage, and subarachnoid hemorrhage.

A two-sample Mendelian randomization (MR) approach was employed. Single nucleotide polymorphisms associated with air pollutants such as NO₂, NO_x, PM_2.5, and PM₁₀ were used as instrumental variables, with summary data sourced from the UK Biobank database. Data for ischemic stroke, intracerebral hemorrhage, and subarachnoid hemorrhage were obtained from the MEGASTROKE project, the International Stroke Genetics Consortium, and the dataset of aneurysmal subarachnoid hemorrhage with European populations in the 2020 genome-wide association study, respectively. The primary analysis method was the inverse variance weighting (IVW) method, with sensitivity analyses conducted using the simple median, weighted median, MR-Egger regression, leave-one-out and MR-PRESSO methods.

The random-effects IVW analysis showed a nominal association between PM_2.5 and subarachnoid hemorrhage, but the confidence interval was wide (OR=5.75, 95%CI: 1.13 – 29.20, P=0.035). After Bonferroni correction, this nominal association was no longer statistically significant. Further sensitivity analyses using MR-PRESSO and leave-one-out methods identified an outlier SNP; after correction for this outlier, the effect estimate substantially decreased and lost statistical significance (OR=2.05, 95%CI: 0.98 – 4.29, P=0.069). No associations were observed between subarachnoid hemorrhage and other air pollutants (NO₂, NO_x, and PM₁₀), and no significant associations were found between any air pollutants and intracerebral hemorrhage or ischemic stroke.

This study found no robust causal association between genetically predicted exposure to common air pollutants (NO₂, NO_x, PM_2.5, and PM₁₀) and the risk of ischemic stroke, intracerebral hemorrhage, or subarachnoid hemorrhage. The nominally significant association between PM_2.5 and subarachnoid hemorrhage was largely driven by an outlier SNP, the signal was mainly driven by an outlier SNP, suggesting hat this genetic variant may act as an effect modifier in gene-environment interactions.