Yang Zhenyu, Xiu Xiaohan, Liu Fengzhao, Li Jixin, Tang Zheng, Zhong Weibo, Xu Shoulei, Ma Shuo, Wang Yating, Zuo Ruixue, Guo Dandan
Heilongjiang University of Chinese Medicine, Harbin, China.
Xiyuan Hospital, China Academy of Chinese Medical Sciences, Beijing, China.
Medicine (Baltimore). 2025 Jul 4;104(27):e43198. doi: 10.1097/MD.0000000000043198.
The 5-year survival rate of patients with heart failure (HF) is comparable to that of malignant tumors, with a persistently high risk of mortality. Atrial fibrillation (AF) is a common cardiac arrhythmia, with its incidence rising annually due to the aging population. Therefore finding relevant therapeutic targets for both diseases is crucial. Firstly, instrumental variables were obtained from publicly available genome-wide association study databases. Secondly, 5 robust Mendelian randomization (MR) methods were employed to assess causal effects between exposure and outcome. Thirdly, we also performed multiple sensitivity analyses and corrected all inverse variance weighted results for false discovery rate (FDR). Fourthly, reverse MR analysis and Mediation MR analysis can improve the completeness of the study. Finally, the protective proteins were analyzed for pathway enrichment and potential drug targets were explored via the DrugBank website. This study identified a total of 23 circulating proteins associated with the diseases, among which defensin beta 135 (DEFB135, PIVW < .001, PFDR = .017) emerged as a shared protective protein against both diseases. Conversely, reverse MR analysis revealed no statistically significant impact of the diseases on these circulating proteins. Mediation MR analysis identified AF as the mediator between DEFB135 and HF. Enrichment analysis elucidated a series of pathways related to HF and AF. Finally, a total of 8 proteins were retrieved from the database. Our MR analysis identified 23 circulating proteins associated with the diseases, providing valuable references for clinical treatment.
心力衰竭（HF）患者的5年生存率与恶性肿瘤相当，死亡率持续居高不下。心房颤动（AF）是一种常见的心律失常，随着人口老龄化，其发病率逐年上升。因此，找到这两种疾病的相关治疗靶点至关重要。首先，从公开的全基因组关联研究数据库中获取工具变量。其次，采用5种稳健的孟德尔随机化（MR）方法评估暴露与结局之间的因果效应。第三，我们还进行了多次敏感性分析，并对所有逆方差加权结果进行了错误发现率（FDR）校正。第四，反向MR分析和中介MR分析可以提高研究的完整性。最后，对保护性蛋白进行通路富集分析，并通过DrugBank网站探索潜在的药物靶点。本研究共鉴定出23种与这两种疾病相关的循环蛋白，其中防御素β135（DEFB135，PIVW < 0.001，PFDR = 0.017）是针对这两种疾病的共同保护性蛋白。相反，反向MR分析显示这两种疾病对这些循环蛋白没有统计学上的显著影响。中介MR分析确定AF是DEFB135和HF之间的中介。富集分析阐明了一系列与HF和AF相关的通路。最后，从数据库中检索到总共8种蛋白。我们的MR分析鉴定出23种与这两种疾病相关的循环蛋白，为临床治疗提供了有价值的参考。
