基于“双心疾病”运用生物信息学及孟德尔随机化探讨重度抑郁与心力衰竭相关性  

Exploring the Association Between Major Depression and Heart Failure Based on"Cardio-Mental Disorders"Using Bioinformatics and Mendelian Randomization

作　　者：朱赟 魏佳明 林瑞芳 刘泳君 李雅[1] 郭志华[1,2,3] ZHU Yun;WEI Jiaming;LIN Ruifang;LIU Yongjun;LI Ya;GUO Zhihua(Hunan University of Chinese Medicine,Changsha 410208,China;Key Laboratory of Traditional Chinese Medicine Intelligent Diagnosis and Treatment of Chronic Diseases at Hunan University of Traditional Chinese Medicine,Changsha 410208,China;Internet+Chronic Disease Chinese Medicine Diagnosis and Treatment and Health Intelligent Application Graduate Joint Training Base,Changsha 410208,China)

机构地区：[1]湖南中医药大学,湖南长沙410208 [2]湖南中医药大学慢病中医智能诊断与治未病湖南省普通高等学校重点实验,湖南长沙410208 [3]互联网+慢病中医诊治与养生智能化应用研究生联合培养基地,湖南长沙410208

出　　处：《中医药信息》2025年第2期1-10,29,共11页Information on Traditional Chinese Medicine

基　　金：国家自然科学基金项目(82174343);湖南省重点研发计划项目(2022SK2012)。

摘　　要：目的:利用生物信息学和孟德尔随机化方法,探讨重度抑郁和心力衰竭之间的相关性、通路基因和潜在治疗靶点。方法:从GEO数据库获取重度抑郁和心力衰竭数据集,筛选差异表达基因(DEGs);对DEGs进行蛋白功能注释(GO)、富集通路(KEGG)分析;利用药物基因交互数据库(DGIdb)寻找潜在治疗药物,并使用miRTarbase、miRDB和TargetScan数据库构建ceRNA网络,分析KEGG预测的通路基因与免疫细胞的相关性;同时以重度抑郁为暴露因素,心力衰竭为结局,选择与重度抑郁显著相关的单核苷酸多态性为工具变量,进行孟德尔随机化分析,并运用相关检验等方法,评价结果的稳定性和可靠性。结果:通过整合重度抑郁和心力衰竭数据集,获得5个DEGs,KEGG发现2个通路基因(HBB、HBA1),并识别出可能同时治疗这两种疾病的药物;miRNAs的分析确定了潜在的治疗靶点(hsa-miR-361-3p),发现免疫细胞中的Monocytes,Neutrophils与2个通路基因相关;孟德尔随机化IVW分析显示,重度抑郁和心力衰竭风险可能存在正向因果关系(P=0.007<0.05,OR=1.169,95%CI:1.044~1.308,β=0.156)。结论:本研究通过孟德尔随机化研究方法证明重度抑郁和心力衰竭风险之间可能存在正向因果关系,并通过生物信息学方法发现两种疾病之间的基因关联。同时鉴定出的基因、药物和潜在治疗靶点为临床诊断及治疗提供了新思路。Objective:To explore the association,pathway genes,and potential therapeutic targets between major depression and heart failure using bioinformatics and Mendelian randomization methods.Methods:Depression and heart failure datasets were obtained from the GEO database,and differentially expressed genes(DEGs)were screened.GO annotation and KEGG pathway enrichment analysis were performed on the DEGs.Potential therapeutic drugs were identified using the Drug-Gene Interaction Database(DGIdb).A ceRNA network was constructed using miRTarbase,miRDB,and TargetScan databases,and the correlation between KEGG predicted pathway genes and immune cells was analyzed.In addition,Mendelian randomization analysis was performed with major depression as the exposure factor and heart failure as the outcome,using significant single nucleotide polymorphisms(SNPs)related to depression as instrumental variables.Correlation tests were also applied to evaluate the stability and reliability of the results.Results:Through integrating the major depression and heart failure datasets,five DEGs were obtained.KEGG analysis identified two pathway genes (HBB, HBA1), and drugs that may treat both diseases simultaneously were identified. miRNA analysis revealed potential therapeutic targets (hsa-miR-361-3p), and found that monocytes and neutrophils in immune cells were associated with the two pathway genes. Mendelian randomization IVW analysis showed a potential positive causal relationship between major depression and heart failure risk (P = 0. 007 < 0. 05, OR = 1. 169, 95%CI: 1. 044-1. 308, β = 0. 156). Conclusion: This study demonstrates a potential positive causal relationship between major depression and heart failure risk using Mendelian randomization. Additionally, bioinformatics methods revealed gene associations between the two diseases. The identified genes, drugs, and potential therapeutic targets provide new insights for clinical diagnosis and treatment.

关 键 词：重度抑郁 心力衰竭 双心疾病 通路基因 孟德尔随机化 生物信息学 

分 类 号：R259[医药卫生—中西医结合] R277.7[医药卫生—中医内科学]