Investigation on the relationship between hemoglobin concentration and stroke risk: a bidirectional Mendelian randomization study

Background: The relationship between hemoglobin concentration and stroke has garnered significant interest in the research community. However, findings from published observational epidemiological studies on this relationship have been inconclusive. By using publicly available genome-wide association study (GWAS) aggregated statistics, a two-sample Mendelian randomization analysis is conducted to explore the causal relationship between hemoglobin concentration and stroke.

Methods: Summary statistics data from UK Biobank for hemoglobin concentration and from the FinnGen R9 and MEGASTROKE consortium for stroke are used. A series of quality control steps are taken to select eligible instrumental SNPs closely related to exposure. In order to make the conclusion more robust and reliable, several robust analysis methods are employed including inverse variance weighted, weighted median, MR-Egger regression, which are based on different assumptions of two-sample MR Analysis. Meanwhile, sensitivity analyses such as pleiotropy test and MR-Egg regression, are performed to mitigate horizontal pleiotropy and heterogeneity.

Results: The two-sample Mendelian randomized study indicates a negative association between hemoglobin concentration and stroke, suggesting that hemoglobin concentration acts as a protective factor against stroke. From the FinnGen database, there is a negative association between hemoglobin concentration and stroke, with an odds ratio (OR) of 0.82 and a 95% confidence interval (CI) of 0.73-0.92, p = 0.0006. Similarly, the MEGASTROKE database findings reinforce this observation. The negative association between hemoglobin concentration and stroke (OR: 0.91, 95%CI: 0.83-1.00, p = 0.040), ischemic stroke (OR: 0.87, 95%CI: 0.79-0.96, p = 0.004), and cardiogenic stroke (OR: 0.82, 95% CI: 0.69-0.99, p = 0.039) further suggests that higher hemoglobin levels might confer a protective effect against these conditions.

Conclusion: Hemoglobin concentration serves as a protective factor against stroke, and managing abnormal hemoglobin levels can effectively reduce the incidence of stroke.