Data_Sheet_1_Investigation on the relationship between hemoglobin concentration and stroke risk: a bidirectional Mendelian randomization study.CSV

BackgroundThe 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.
MethodsSummary 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.
ResultsThe 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.
ConclusionHemoglobin concentration serves as a protective factor against stroke, and managing abnormal hemoglobin levels can effectively reduce the incidence of stroke.

研究背景
血红蛋白浓度与脑卒中之间的关联一直受到学界的广泛关注。然而，已发表的相关观察性流行病学研究结论尚未达成一致。本研究利用公开获取的全基因组关联研究（genome-wide association study, GWAS）汇总统计数据，采用两样本孟德尔随机化分析方法，探究血红蛋白浓度与脑卒中之间的因果关联。

研究方法
本研究使用英国生物银行（UK Biobank）中血红蛋白浓度的汇总统计数据，以及芬根R9（FinnGen R9）数据库和MEGASTROKE联盟的脑卒中相关数据。本研究通过一系列质量控制步骤，筛选出与暴露因素（血红蛋白浓度）密切相关的合格工具单核苷酸多态性位点（Single Nucleotide Polymorphism, SNP）。为保障研究结论的稳健性与可靠性，本研究采用了基于两样本孟德尔随机化分析不同假设的多种稳健分析方法，包括逆方差加权法、加权中位数法以及MR-Egger回归。同时，为减轻水平多效性和异质性带来的偏倚，本研究还开展了多效性检验、MR-Egger回归等敏感性分析。

研究结果
本两样本孟德尔随机化研究显示，血红蛋白浓度与脑卒中之间呈负相关，提示血红蛋白浓度是脑卒中的保护因素。来自芬根数据库的分析结果表明，血红蛋白浓度与脑卒中呈负相关，比值比（odds ratio, OR）为0.82，95%置信区间（confidence interval, CI）为0.73~0.92，p值为0.0006。同样，MEGASTROKE数据库的分析结果也印证了这一发现：血红蛋白浓度与脑卒中（OR=0.91，95%CI=0.83~1.00，p=0.040）、缺血性脑卒中（OR=0.87，95%CI=0.79~0.96，p=0.004）以及心源性脑卒中（OR=0.82，95%CI=0.69~0.99，p=0.039）均呈负相关，进一步表明较高的血红蛋白水平可对上述疾病起到保护作用。

研究结论
血红蛋白浓度是脑卒中的保护因素，干预异常血红蛋白水平可有效降低脑卒中的发病风险。