Associations of genetically predicted Helicobacter pylori antibodies with aneurysmal subarachnoid hemorrhage and unruptured intracranial aneurysm: A two-sample mendelian randomization study.

The causal relationship between Helicobacter pylori antibodies and the risk of cerebral aneurysms remains unclear. We used Mendelian randomization analysis to assess the causal relationship between Helicobacter pylori antibodies and the risk of cerebral aneurysms. A genome-wide association study (GWAS) dataset from the IEU Open GWAS project was utilized for antibodies to 7 different Helicobacter pylori-specific proteins, and from the Finnish database for cerebral aneurysms that included unruptured aneurysm (uIA) and aneurysmal subarachnoid hemorrhage (aSAH). Mendelian randomization (MR) analysis was used to evaluate the causal relationship between Helicobacter pylori antibodies and cerebral aneurysms. Multivariable Mendelian randomization was used to assess whether the VacA-aSAH association persisted after adjustment for systolic blood pressure, dietary magnesium intake, and dietary calcium intake. A Bonferroni-corrected significance threshold of P < .0036 was applied to the 14 primary comparisons. Genetically predicted serum antibody levels of Helicobacter pylori (H. pylori) vacuolating cytotoxin-A (VacA) showed a nominal inverse association with aSAH (odds ratio (OR) = 0.88, 95% CI: 0.78-0.99, P = .044), but were not associated with uIA. However, this association did not remain statistically significant after Bonferroni correction. Other H. pylori antibodies were not causally associated with aSAH and uIA. In the MVMR analyses, the VacA-aSAH association was no longer statistically significant after adjustment for systolic blood pressure or dietary calcium intake, whereas it remained nominally significant after adjustment for dietary magnesium intake. These findings indicate changes after adjustment but do not establish mediation. Our study suggests that increased levels of serum Helicobacter pylori vacuolating cytotoxin-A (VacA) antibodies may be inversely associated with aneurysmal subarachnoid hemorrhage (aSAH). The attenuation of the association after adjustment for systolic blood pressure and dietary calcium intake suggests that these factors may partly account for the observed association, although mediation cannot be confirmed. These preliminary findings require external validation in independent populations and larger GWAS datasets before clinical implications can be considered.