基于孟德尔随机化探究情绪波动与肝硬化相关性及中药预测OA
Exploration on the Relationship Between Mood Swings and Liver Cirrhosis Based on Mendelian Randomization and Chinese Materia Medica Prediction
目的 探究情绪波动与肝硬化的因果关系,并预测对其有潜在调控作用的中药,为肝硬化的中医药治疗提供思路.方法 利用公开的全基因组关联分析(GWAS)基因数据,采用双样本、双向、多变量孟德尔随机化方法分析情绪波动与肝硬化的因果关系,并检验异质性和水平多效性.查询单核苷酸多态性(SNPs)邻近靶点的有效化学成分进行中药预测,统计分析其性味归经和功效.通过Cytoscape软件构建靶点-有效成分-中药网络,使用Centiscape、MCODE插件筛选核心中药.结果 以情绪波动为暴露因素、肝硬化为结局的孟德尔随机化分析显示正向因果关系(IVW OR=2.361 1,95%CI:1.106 0~5.040 4).SNPs间无异质性、水平多效性和离群值,敏感性良好.双向孟德尔随机化分析显示情绪波动与肝硬化无双向因果关联,多变量孟德尔随机化方法分析显示,在考虑病毒性肝炎和自身免疫性肝炎等混杂因素情况下,情绪波动与肝硬化存在正向因果关系.筛选出28个关键靶点、35种有效化学成分,与640味药物存在映射关系.相关药物以温、寒、平性,甘、苦、辛味为主,主要归肝经、肺经、脾经,功效以清热解毒、凉血止血、利水消肿为主.网络分析筛选出核心药物为郁金、姜黄、灵芝.结论 本研究提示情绪波动可能增加肝硬化风险,并预测郁金、姜黄、灵芝为潜在核心药物,为肝硬化的中医药治疗与新药研发提供参考.
Objective To investigate the causal relationship between mood swings and liver cirrhosis;To predict the potential regulatory effect of Chinese materia medica;To provide ideas for the TCM treatment of liver cirrhosis.Methods With publicly available genome-wide association study(GWAS)data,a two-sample,bidirectional,multivariate Mendelian randomization(MR)approach was employed to examine the causality between mood swings and liver cirrhosis and to assess heterogeneity and horizontal pleiotropy.Single nucleotide polymorphisms(SNPs)were queried to identify effective chemical components for Chinese materia medica prediction.The properties,tastes,meridian tropism and efficacy of these Chinese materia medica were statistically analyzed.A network of target-active component-Chinese materia medica was constructed using Cytoscape software,with core Chinese materia medica identified via the Centiscape and MCODE plugins.Results MR analysis revealed a positive causal relationship between mood swings(exposure)and liver cirrhosis(outcome)(IVW OR=2.361 1,95%CI:1.106 0-5.040 4).There was no heterogeneity,level pleiotropy and outliers among SNPs,and the sensitivity was good.Two-way MR analysis showed that there was no two-way causal relationship between mood swings and liver cirrhosis.Multivariate MR analysis showed that there was a positive causal relationship between mood swings and liver cirrhosis when considering the confounding factors of viral hepatitis and autoimmune hepatitis.A total of 28 key targets were identified,yielding 35 active chemical components,mapping relationship with 640 kinds of Chinese materia medica.The main properties were warm,cold and neutral;the main tastes were sweet,bitter and pungent;the meridian tropism primarily involved the liver,lung and spleen meridians;the primary efficacy included clearing heat-toxicity,cooling the blood and stanching bleeding,and promoting diuresis to alleviate edema.Network analysis identified Curcumae Radix,Curcumae Longae Rhizoma and Ganoderma as the core Chinese materia medica.Conclusion This study suggests that mood swings may increase the risk of liver cirrhosis and identifies Curcumae Radix,Curcumae Longae Rhizoma and Ganoderma as potential core Chinese materia medica,providing references for TCM treatment and new drug development for liver cirrhosis.
徐子皓;刘逸藩;徐俊;程良斌
湖北中医药大学中医临床学院,湖北 武汉 430061湖北中医药大学中医临床学院,湖北 武汉 430061湖北中医药大学,湖北 武汉 430061湖北中医药大学,湖北 武汉 430061
医药卫生
肝硬化情绪波动孟德尔随机化中药预测单核苷酸多态性
liver cirrhosismood swingsMendelian randomizationChinese materia medica predictionsingle nucleotide polymorphisms
《中国中医药信息杂志》 2026 (1)
57-63,7
国家自然科学基金(82274367)
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