Chen Qian, Shou Weiling, Zhang Li, Fang Jiaying, Guo Ye
Department of Clinical Laboratory, Peking Union Medical College Hospital, Chinese Academy of Medical Science and Peking Union Medical College, Beijing, 100730, China.
Sci Rep. 2025 May 3;15(1):15549. doi: 10.1038/s41598-025-00203-2.
This study investigates the causal association between genetic prediction of iron status and subarachnoid hemorrhage (SAH). A two-sample MR analysis was conducted using genome-wide association study (GWAS) summary data for four iron biomarkers: serum iron, serum ferritin, total iron-binding capacity (TIBC), and transferrin saturation (TSAT). Genetic variants were selected as instrumental variables (IVs) to minimize confounding. Causal estimates were obtained using inverse variance weighting (IVW), MR-Egger, weighted median, and weighted mode methods. Sensitivity analyses, including Cochran's Q-test, MR-Egger regression, MR-PRESSO, and leave-one-out analysis, were performed to assess heterogeneity and pleiotropy. IVW analysis revealed a significant association between increased genetically predicted TIBC and higher SAH risk (OR = 1.71, 95% CI: 1.21-2.41, P = 0.002), while higher TSAT was associated with lower SAH risk (OR = 0.76, 95% CI: 0.62-0.93, P = 0.01). No causal association was found between serum iron, serum ferritin, and SAH. Sensitivity analyses confirmed the robustness of the results, with no evidence of horizontal pleiotropy. However, heterogeneity was detected in serum ferritin, suggesting potential variability in its effect. This MR study provides genetic evidence for the causal relationship between TIBC, TSAT, and SAH risk. These findings highlight the potential role of iron metabolism in SAH pathophysiology, warranting further investigation.
本研究调查铁状态的基因预测与蛛网膜下腔出血（SAH）之间的因果关联。使用四种铁生物标志物（血清铁、血清铁蛋白、总铁结合力（TIBC）和转铁蛋白饱和度（TSAT））的全基因组关联研究（GWAS）汇总数据进行了两样本孟德尔随机化（MR）分析。选择基因变异作为工具变量（IVs）以尽量减少混杂因素。使用逆方差加权（IVW）、MR-Egger、加权中位数和加权模式方法获得因果估计值。进行了敏感性分析，包括 Cochr an's Q检验、MR-Egger回归、MR-PRESSO和留一法分析，以评估异质性和多效性。IVW分析显示，基因预测的TIBC升高与SAH风险升高之间存在显著关联（OR = 1.71，95%CI：1.21 - 2.41，P = 0.002），而较高的TSAT与较低的SAH风险相关（OR = 0.76，95%CI：0.62 - 0.93，P = 0.01）。未发现血清铁、血清铁蛋白与SAH之间存在因果关联。敏感性分析证实了结果的稳健性，没有水平多效性的证据。然而，在血清铁蛋白中检测到异质性，表明其效应可能存在变异性。这项MR研究为TIBC、TSAT与SAH风险之间的因果关系提供了遗传学证据。这些发现突出了铁代谢在SAH病理生理学中的潜在作用，值得进一步研究。
