■观察性临床研究表明,扩张型心肌病(DCM)与各种因素之间存在关联,包括肌动蛋白,心肌肌钙蛋白I(CTnI),desmocollin-2,围产期,酗酒,Behçet病,系统性红斑狼疮,甲状腺功能亢进和甲状腺毒症,甲状腺功能减退,肉碱代谢紊乱,和肾功能不全。这些关联的因果关系仍然不确定。本研究旨在使用孟德尔随机化(MR)方法探索这些相关性。
■通过孟德尔随机分析研究DCM的病因。
■数据挖掘在全基因组关联研究数据库中进行,专注于变异靶蛋白(Titin,CTnI,desmocollin-2),围产期,酗酒,Behçet病,系统性红斑狼疮,甲状腺功能亢进和甲状腺毒症,甲状腺功能减退,肉碱代谢紊乱,肾功能不全,以DCM为结果。分析采用了各种回归模型,即,逆方差加权(IVW),MR-Egger,简单模式,加权中位数,和加权模式方法。
■IVW结果显示肌动蛋白与DCM之间存在相关性,确定Titin为保护因子[OR=0.856,95%CI(0.744-0.985),P=0.030]。CTnI蛋白与DCM相关,将其标记为风险因素[OR=1.204,95%CI(1.010-1.436),P=0.040]。Desmocollin-2也与DCM相关,被认为是危险因素[OR=1.309,95%CI(1.085-1.579),P=0.005]。然而,围产期之间没有因果关系,酗酒,Behçet病,系统性红斑狼疮,甲状腺功能亢进和甲状腺毒症,甲状腺功能减退,肉碱代谢紊乱,肾功能不全,和DCM(P>0.05)。MR-Egger截距试验显示无多效性(P>0.05),肯定孟德尔随机化在因果推断中的有效性。
■Titin,CTnI,和桥蛋白2蛋白被确定为DCM的独立危险因素。与以前的观察性研究相比,未观察到DCM与围产期之间的因果关系,酗酒,Behçet病,系统性红斑狼疮,甲状腺功能亢进和甲状腺毒症,甲状腺功能减退,肉碱代谢紊乱,或肾功能不全。
UNASSIGNED: Observational clinical studies suggest an association between dilated cardiomyopathy (DCM) and various factors including titin, cardiac troponin I (CTnI), desmocollin-2, the perinatal period, alcoholism, Behçet\'s disease, systemic lupus erythematosus, hyperthyroidism and thyrotoxicosis, hypothyroidism, carnitine metabolic disorder, and renal insufficiency. The causal nature of these associations remains uncertain. This study aims to explore these correlations using the Mendelian randomization (MR) approach.
UNASSIGNED: To investigate the etiology of DCM through Mendelian randomization analysis.
UNASSIGNED: Data mining was conducted in genome-wide association study databases, focusing on variant target proteins (titin, CTnI, desmocollin-2), the perinatal period, alcoholism, Behçet\'s disease, systemic lupus erythematosus, hyperthyroidism and thyrotoxicosis, hypothyroidism, carnitine metabolic disorder, and renal insufficiency, with DCM as the outcome. The analysis employed various regression models, namely, the inverse-variance weighted (IVW), MR-Egger, simple mode, weighted median, and weighted mode methods.
UNASSIGNED: The IVW results showed a correlation between titin protein and DCM, identifying titin as a protective factor [OR = 0.856, 95% CI (0.744-0.985), P = 0.030]. CTnI protein correlated with DCM, marking it as a risk factor [OR = 1.204, 95% CI (1.010-1.436), P = 0.040]. Desmocollin-2 also correlated with DCM and was recognized as a risk factor [OR = 1.309, 95% CI (1.085-1.579), P = 0.005]. However, no causal relationship was found between the perinatal period, alcoholism, Behçet\'s disease, systemic lupus erythematosus, hyperthyroidism and thyrotoxicosis, hypothyroidism, carnitine metabolic disorder, renal insufficiency, and DCM (P > 0.05). The MR-Egger intercept test indicated no pleiotropy (P > 0.05), affirming the effectiveness of Mendelian randomization in causal inference.
UNASSIGNED: Titin, CTnI, and desmocollin-2 proteins were identified as independent risk factors for DCM. Contrasting with previous observational studies, no causal relationship was observed between DCM and the perinatal period, alcoholism, Behçet\'s disease, systemic lupus erythematosus, hyperthyroidism and thyrotoxicosis, hypothyroidism, carnitine metabolic disorder, or renal insufficiency.