No genetic association between iron deficiency anemia and ischemic stroke and its subtypes: a bidirectional two-sample Mendelian randomization study

Background Observational researches have suggested a connection between iron deficiency anemia (IDA) and an increased likelihood of ischemic stroke (IS), yet establishing causality is challenging owing to the inherent limitations of such studies, including their vulnerability to confounding factors and the potential for reverse causation. This study employs a bidirectional two-sample Mendelian randomization (MR) approach to assess the causal linkage between IDA and IS and its subtypes. Methods Identifiable single nucleotide polymorphisms (SNPs) with significant links to either IDA or IS and its subtypes were employed as instrumental variables (IVs). The relationship between IDA and any IS, small vessel stroke (SVS), cardioembolic stroke (CES), and large artery stroke (LAS), was quantified using the inverse variance weighted (IVW) method. Complementary analyses utilizing MR-Egger and weighted median methods further supplemented the IVW findings. Moreover, the leave-one-out analysis, MR-Egger intercept test, MR-PRESSO global test, and Cochrane's Q test were conducted for sensitivity analyses. Results This study revealed no correlation between IDA and any IS (IVW method: OR [95% CI] = 0.977 [0.863-1.106]; p = 0.716), LAS (OR [95% CI] = 1.158 [0.771-1.740]; p = 0.479), CES (OR [95% CI] = 1.065 [0.882-1.285]; p = 0.512), or SVS (OR [95% CI] = 1.138 [0.865-1.498]; p = 0.357). Conducting a reverse MR analysis, it was determined that there is no causal connection between any IS, LAS, CES, SVS, and IDA (all p > 0.05). Sensitivity analysis indicated that heterogeneity was not significant and no evidence of horizontal pleiotropy was detected. Conclusion This MR study suggested no causal effect of IDA on IS, LAS, CES, and SVS. Through reverse MR analyses, it was determined that IS and its subtypes did not exert a causal impact on IDA.