Iron status and risk of aneurysmal subarachnoid hemorrhage: evidence from a two-sample Mendelian randomization

Observational studies have reported associations between iron status and aneurysmal subarachnoid hemorrhage (aSAH) and its complications. However, the causal relationship between these factors remains unclear. This Mendelian Randomization (MR) study adhered to the Strengthening Reporting of Observational Studies in Epidemiology using Mendelian Randomization (STROBE-MR) guidelines. Data for iron status and aneurysmal subarachnoid hemorrhage (aSAH) were sourced from genome-wide association studies (GWAS) available in public databases. The primary MR analysis was conducted using the inverse variance weighted (IVW) random-effects models. To ensure the robustness of the causal inferences, we performed sensitivity analyses. The effects from various analytical models and heterogeneity were visualized using scatter plots and funnel plots, respectively. Our analysis supported a causal association under MR assumptions between iron status and aSAH. Specifically, transferrin saturation (TSAT) was associated with a decreased risk of aSAH (OR = 0.726, 95% CI: 0.568–0.927, P = 0.010), while total iron-binding capacity (TIBC) was associated with an increased risk (OR = 1.989, 95% CI: 1.301–3.042, P = 0.002). No causal association was identified between iron or ferritin levels and aSAH. Additionally, reverse MR analysis indicated no causal relationship between aSAH and iron status. Under MR assumptions, our study supports a causal association between iron-status markers (TSAT, TIBC) and aSAH. Clinical implications require prospective validation.