Causal associations between neuroinflammation-related genes and intracerebral hemorrhage: an integrated study of Mendelian Randomization and gene functional analysis.
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引用次数: 0
Abstract
Aim: Intracerebral hemorrhage (ICH) is a life-threatening stroke subtype where neuroinflammation plays a crucial role. However, the genetic basis for neuroinflammation in ICH remains unclear.
Methods: This study used Mendelian Randomization (MR) to investigate the causal impact of neuroinflammation-related genes on ICH risk. A two-sample MR analysis was conducted using genetic variants from large-scale genome-wide association studies (GWAS). The primary analytical methods included the inverse variance weighted (IVW) approach, supplemented by MR-Egger regression and the weighted median method. Protein-protein interaction (PPI) network analysis, Gene Ontology (GO) enrichment analysis, and Gene Set Enrichment Analysis (GSEA) were employed to explore the biological mechanisms underlying these associations.
Results: Elevated expression of the CHUK gene was significantly associated with increased ICH risk (OR = 1.17, 95% CI 1.02-1.35, p = 0.0245 in the Ebi-ICH dataset; OR = 1.25, 95% CI 1.03-1.52, p = 0.0252 in the Finn-ICH dataset). Similarly, the CTLA4 gene showed a strong association with ICH (OR = 1.29, 95% CI 1.10-1.52, p < 0.01 in the Ebi-ICH dataset; OR = 1.23, 95% CI 1.02-1.47, p = 0.0264 in the Finn-ICH dataset). These results suggest that these genes contribute to ICH through mechanisms involving the NF-κB signaling pathway and immune regulation.
Conclusion: The findings reveal a significant genetic influence of CHUK and CTLA4 on ICH risk, provide potential targets for future therapeutic interventions, which could lead to the development of more effective treatment strategies for ICH.
目的：脑出血（ICH）是一种危及生命的中风亚型，其中神经炎症起着至关重要的作用。然而，脑出血神经炎症的遗传基础仍不清楚。方法：本研究采用孟德尔随机化方法（MR）研究神经炎症相关基因对脑出血风险的因果影响。使用来自大规模全基因组关联研究（GWAS）的遗传变异进行了两样本MR分析。主要分析方法为方差反加权法（IVW），辅以MR-Egger回归和加权中位数法。利用蛋白-蛋白相互作用（PPI）网络分析、基因本体（GO）富集分析和基因集富集分析（GSEA）来探讨这些关联的生物学机制。结果：CHUK基因表达升高与脑出血风险增加显著相关（OR = 1.17, 95% CI 1.02-1.35, p = 0.0245）；OR = 1.25, 95% CI 1.03-1.52, p = 0.0252 （Finn-ICH数据集）。同样，CTLA4基因与ICH有很强的相关性（OR = 1.29, 95% CI 1.10-1.52, p < 0.01）；OR = 1.23, 95% CI 1.02-1.47, p = 0.0264 （Finn-ICH数据集）。这些结果表明，这些基因通过涉及NF-κB信号通路和免疫调节的机制参与脑出血。结论：这些发现揭示了CHUK和CTLA4对脑出血风险的显著遗传影响，为未来的治疗干预提供了潜在的靶点，这可能导致脑出血更有效的治疗策略的发展。
期刊介绍：
The International Journal of Neuroscience publishes original research articles, reviews, brief scientific reports, case studies, letters to the editor and book reviews concerned with problems of the nervous system and related clinical studies, epidemiology, neuropathology, medical and surgical treatment options and outcomes, neuropsychology and other topics related to the research and care of persons with neurologic disorders. The focus of the journal is clinical and transitional research. Topics covered include but are not limited to: ALS, ataxia, autism, brain tumors, child neurology, demyelinating diseases, epilepsy, genetics, headache, lysosomal storage disease, mitochondrial dysfunction, movement disorders, multiple sclerosis, myopathy, neurodegenerative diseases, neuromuscular disorders, neuropharmacology, neuropsychiatry, neuropsychology, pain, sleep disorders, stroke, and other areas related to the neurosciences.
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