Zhang Yifei, Guo Chenyuan, Wang Lanxin, Wu Lei, Lv Jia, Huang Xia, Yang Wuxiao
The Cardiology Department of Shanxi Provincial People's Hospital, Shanxi Medical University, Taiyuan, Shanxi, China.
The Oncology Department of Shanxi Provincial People's Hospital, Shanxi Medical University, Taiyuan, Shanxi, China.
Br J Hosp Med (Lond). 2025 Jan 24;86(1):1-19. doi: 10.12968/hmed.2024.0504. Epub 2025 Jan 14.
Research evidence has demonstrated a significant association between hypertrophic cardiomyopathy (HCM) and atrial fibrillation (AF), but the causality and pattern of this link remain unexplored. Therefore, this study investigated the causal relationship between HCM and AF using a two-sample and bidirectional Mendelian randomization (MR) approach. Additionally, this assessed the role of cardiovascular proteins (CPs) associated with cardiovascular diseases between HCM and AF by applying a two-step MR analysis. Data for HCM, AF, and 90 CPs were obtained from the Finn Gen and IEU Open GWAS Project databases. MR-Egger, inverse variance weighting (IVW), weighted median estimator (WME), weighted mode, and simple mode were used to estimate causal inferences. Furthermore, Cochran's Q test, MR-Egger's intercept terms, and Leave-one-out methods determined the heterogeneity, horizontal pleiotropy, and sensitivity. Additionally, mediation effects were used to assess the role of CPs in the relationship between HCM and AF. Two-sample and bidirectional MR analysis revealed HCM as a risk factor for AF (odds ratio (OR) = 1.008, 95% confidence interval (CI): 1.001-1.016, = 0.029) and AF was found to increase the risk of developing HCM (OR = 1.145, 95% CI: 0.963-1.361, = 0.126). Moreover, Two-step MR analyses indicated that 5 CPs were causally associated with HCM; 12 CPs with AF and 1 CP (Melusin) with both HCM and AF. Additionally, Melusin was observed as a protective factor for both HCM and AF and may serve as a mediator variable for these two conditions (mediation effect 0.0004, mediation ratio 5.5178%, 95% CI: 5.4624-5.5731). HCM may increase the risk of developing AF, with Melusin serving as a mediator for this risk.
研究证据表明肥厚型心肌病（HCM）与心房颤动（AF）之间存在显著关联，但这种联系的因果关系和模式仍未得到探索。因此，本研究采用两样本双向孟德尔随机化（MR）方法研究了HCM与AF之间的因果关系。此外，通过应用两步MR分析，评估了与HCM和AF之间心血管疾病相关的心血管蛋白（CPs）的作用。来自芬兰基因数据库和IEU开放全基因组关联研究（GWAS）项目数据库的HCM、AF和90种CPs的数据。采用MR-Egger、逆方差加权（IVW）、加权中位数估计器（WME）、加权模式和简单模式来估计因果推断。此外，Cochran's Q检验、MR-Egger的截距项和留一法确定了异质性、水平多效性和敏感性。此外，中介效应用于评估CPs在HCM与AF关系中的作用。两样本双向MR分析显示HCM是AF的一个危险因素（优势比（OR）=1.008，95%置信区间（CI）：1.001-1.016，P=0.029），并且发现AF会增加发生HCM的风险（OR = 1.145，95% CI：0.963-1.361，P = 0.126）。此外，两步MR分析表明，5种CPs与HCM存在因果关联；12种CPs与AF存在因果关联，1种CP（Melusin）与HCM和AF均存在因果关联。此外，Melusin被视为HCM和AF的保护因素，可能是这两种疾病的中介变量（中介效应0.0004，中介比例5.5178%，95% CI：5.4624-5.5731）。HCM可能会增加发生AF的风险，Melusin是这种风险的中介因素。
