基因洞察细胞因子-血栓串扰:综合多组学网络分析

IF 3.4 3区 医学 Q1 HEMATOLOGY
Wei Zhou , Xiaoyi Qin , Honglei Xu , Jingye Pan
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引用次数: 0

摘要

血栓性疾病(TDs)共有的和独特的机制尚不清楚。本研究通过多组学整合探索炎症细胞因子与TDs之间的因果关系,以确定靶向治疗方案。方法采用两样本孟德尔随机化(MR)方法,利用三种遗传工具评估47种细胞因子对13种TD性状的因果关系。研究结果通过共定位、复制和转录组分析得到验证。两步磁共振评估了1400种代谢物和731种免疫细胞的中介作用。系统评估td相关细胞因子的可用药性和感染相关的多效性。结果初步MR鉴定出86对细胞因子- td相关对,其中21对证据支持可接受,可作为进一步分析的枢纽对。共定位证据出现了两对,而复制一致性是稳健的。15个细胞因子基因- td对中有5个显示差异表达,与MR效应一致。中介分析显示,五种代谢物和免疫细胞亚型调节细胞因子- td通路。四种细胞因子对血栓形成有治疗前景,而六种细胞因子对TDs和感染有双重作用。我们的综合分析揭示了炎症-血栓相互作用的共同和自主机制,并确定了细胞因子介导的治疗靶点,可以避免标准抗血栓治疗相关的出血并发症。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

Genetic insights into cytokine-thrombosis cross-talk: an integrated multi-omics network analysis

Genetic insights into cytokine-thrombosis cross-talk: an integrated multi-omics network analysis

Background

The mechanisms shared and unique to thrombotic diseases (TDs) remain unclear. This study explores the causal relationships between inflammatory cytokines and TDs via multi-omics integration to identify targeted therapeutic alternatives.

Methods

We conducted two-sample Mendelian randomization (MR) using three genetic instruments to evaluate the causal effects of 47 cytokines on 13 TD traits. Findings were validated through colocalization, replication, and transcriptomic analyses. Two-step MR assessed mediation effects of 1400 metabolites and 731 immune cells. Druggability and infection-related pleiotropy of TD-associated cytokines were systematically evaluated.

Results

Primary MR identified 86 cytokine-TD correlated pairs, with 21 pairs providing acceptable evidence support, meriting their designation as hub pairs for further analysis. Colocalization evidence emerged for two pairs, whereas replication consistency was robust. Five of the 15 cytokine gene-TD pairs revealed differential expression, aligning with the MR effects. Mediation analyses showed five metabolites and immune cell subtypes modulating cytokine-TD pathways. Four cytokines exhibited therapeutic promise for thrombosis, whereas six showed dual effects on TDs and infections.

Conclusions

Our integrated analysis reveals shared and autonomous mechanisms governing inflammatory-thrombotic interactions and identifies a cytokine-mediated therapeutic target that may avoid bleeding complications linked to standard antithrombotic therapy.
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来源期刊
Thrombosis research
Thrombosis research 医学-外周血管病
CiteScore
14.60
自引率
4.00%
发文量
364
审稿时长
31 days
期刊介绍: Thrombosis Research is an international journal dedicated to the swift dissemination of new information on thrombosis, hemostasis, and vascular biology, aimed at advancing both science and clinical care. The journal publishes peer-reviewed original research, reviews, editorials, opinions, and critiques, covering both basic and clinical studies. Priority is given to research that promises novel approaches in the diagnosis, therapy, prognosis, and prevention of thrombotic and hemorrhagic diseases.
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