Identification of Alzheimer's disease susceptibility genes by the integration of genomics and transcriptomics.

IF 1.7 4区医学 Q3 CLINICAL NEUROLOGY

Neurological Research Pub Date : 2025-05-07 DOI:10.1080/01616412.2025.2499890

Chenghong OuYang, Hanping Shi, Zhiying Lin

{"title":"Identification of Alzheimer's disease susceptibility genes by the integration of genomics and transcriptomics.","authors":"Chenghong OuYang, Hanping Shi, Zhiying Lin","doi":"10.1080/01616412.2025.2499890","DOIUrl":null,"url":null,"abstract":"Background: Alzheimer's disease (AD) is a progressive neurodegenerative disease. With the deepening of clinical and genomic research, a series of biomarkers and risk factors related to AD have been identified. However, the exact molecular mechanism of AD is not completely understood.Methods: By combining expression quantitative trait loci (eQTLs) analysis with the results of genome-wide association studies (GWAS), the candidate genes (CG) related to AD were screened out accurately. We identified that intersection genes of differentially expressed genes (DEGs) and CG are the key genes. Then, GO, KEGG, and GSEA were utilized for functional enrichment analysis. Finally, we predicted AD responses to immunotherapy by the single sample gene set enrichment analysis (ssGSEA).Results: A total of 253 DEGs were identified. The three key genes (VASP, SURF2, and TARBP1) were identified by taking the intersection of DEGs and CG. Through Mendelian randomization (MR) analysis, it was found that the risk of AD was significantly increased when VASP expression increased (OR = 0.1.046), while the risk of AD was significantly decreased when SURF2 (OR = 0.897) and TARBP1(OR = 0.920) expression increased. Subsequently, the functional analysis indicated that the core genes were mainly enriched in Leukocyte Transendothelial Migration, cGMP-PKG signaling pathway, and Rap1 signaling pathway. Through ssGSEA analysis showed that all three core genes were significantly related to M2 macrophages.Conclusions: Three core genes were screened by integrating eQTLs data, GWAS data and transfer group data, and the potential mechanism of diagnosis and treatment of AD was revealed.","PeriodicalId":19131,"journal":{"name":"Neurological Research","volume":" ","pages":"1-13"},"PeriodicalIF":1.7000,"publicationDate":"2025-05-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Neurological Research","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1080/01616412.2025.2499890","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q3","JCRName":"CLINICAL NEUROLOGY","Score":null,"Total":0}

引用次数: 0

Abstract

Background: Alzheimer's disease (AD) is a progressive neurodegenerative disease. With the deepening of clinical and genomic research, a series of biomarkers and risk factors related to AD have been identified. However, the exact molecular mechanism of AD is not completely understood.

Methods: By combining expression quantitative trait loci (eQTLs) analysis with the results of genome-wide association studies (GWAS), the candidate genes (CG) related to AD were screened out accurately. We identified that intersection genes of differentially expressed genes (DEGs) and CG are the key genes. Then, GO, KEGG, and GSEA were utilized for functional enrichment analysis. Finally, we predicted AD responses to immunotherapy by the single sample gene set enrichment analysis (ssGSEA).

Results: A total of 253 DEGs were identified. The three key genes (VASP, SURF2, and TARBP1) were identified by taking the intersection of DEGs and CG. Through Mendelian randomization (MR) analysis, it was found that the risk of AD was significantly increased when VASP expression increased (OR = 0.1.046), while the risk of AD was significantly decreased when SURF2 (OR = 0.897) and TARBP1(OR = 0.920) expression increased. Subsequently, the functional analysis indicated that the core genes were mainly enriched in Leukocyte Transendothelial Migration, cGMP-PKG signaling pathway, and Rap1 signaling pathway. Through ssGSEA analysis showed that all three core genes were significantly related to M2 macrophages.

Conclusions: Three core genes were screened by integrating eQTLs data, GWAS data and transfer group data, and the potential mechanism of diagnosis and treatment of AD was revealed.

查看原文本刊更多论文

结合基因组学和转录组学鉴定阿尔茨海默病易感基因。

背景：阿尔茨海默病（AD）是一种进行性神经退行性疾病。随着临床和基因组研究的深入，一系列与AD相关的生物标志物和危险因素被发现。然而，阿尔茨海默病的确切分子机制尚不完全清楚。方法：将表达数量性状位点（eqtl）分析与全基因组关联研究（GWAS）结果相结合，准确筛选出AD相关候选基因（CG）。我们发现差异表达基因（DEGs）和CG的交叉基因是关键基因。然后利用GO、KEGG和GSEA进行功能富集分析。最后，我们通过单样本基因集富集分析（ssGSEA）预测了AD对免疫治疗的反应。结果：共鉴定出253个deg。三个关键基因（VASP， SURF2和TARBP1）通过DEGs和CG的交叉鉴定。通过孟德尔随机化（Mendelian randomization， MR）分析发现，VASP表达增加时AD的风险显著增加（OR = 0.1.046），而SURF2 （OR = 0.897）和TARBP1（OR = 0.920）表达增加时AD的风险显著降低。随后的功能分析表明，核心基因主要富集于白细胞跨内皮迁移、cGMP-PKG信号通路和Rap1信号通路。通过ssGSEA分析，三个核心基因均与M2巨噬细胞有显著相关。结论：通过整合eQTLs数据、GWAS数据和转移组数据，筛选出3个核心基因，揭示AD诊断和治疗的潜在机制。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

求助全文

约1分钟内获得全文求助全文

来源期刊

Neurological Research 医学-临床神经学

CiteScore

3.60

自引率

0.00%

发文量

116

审稿时长

5.3 months

期刊介绍： Neurological Research is an international, peer-reviewed journal for reporting both basic and clinical research in the fields of neurosurgery, neurology, neuroengineering and neurosciences. It provides a medium for those who recognize the wider implications of their work and who wish to be informed of the relevant experience of others in related and more distant fields. The scope of the journal includes: •Stem cell applications •Molecular neuroscience •Neuropharmacology •Neuroradiology •Neurochemistry •Biomathematical models •Endovascular neurosurgery •Innovation in neurosurgery.