Genome-Wide Identification of Cell Type-Specific Susceptibility Genes for SLE Through the Analysis of RNA Modification-Associated SNPs.

IF 2.9 4区 医学 Q3 IMMUNOLOGY Immunological Investigations Pub Date : 2024-11-01 Epub Date: 2024-09-04 DOI:10.1080/08820139.2024.2399577
Huan Zhang, Kedi Fan, Yuxi Chen, Peng Xu, Zhentao Zhang, Xingbo Mo, Yufan Guo
{"title":"Genome-Wide Identification of Cell Type-Specific Susceptibility Genes for SLE Through the Analysis of RNA Modification-Associated SNPs.","authors":"Huan Zhang, Kedi Fan, Yuxi Chen, Peng Xu, Zhentao Zhang, Xingbo Mo, Yufan Guo","doi":"10.1080/08820139.2024.2399577","DOIUrl":null,"url":null,"abstract":"<p><strong>Introduction: </strong>This study aimed to elucidate the functional genes associated with systemic lupus erythematosus (SLE) in various cell types through the utilization of RNAm-SNPs.</p><p><strong>Methods: </strong>Utilizing large-scale genetic data, we identified associations between RNAm-SNPs and SLE. The association between RNAm-SNPs and bulk and single-cell mRNA expression (eQTL) and protein levels (pQTL) were examined. Mendelian randomization and differential expression analyses were conducted to explore the links between gene expression, protein levels, and SLE.</p><p><strong>Results: </strong>We identified 41 RNAm-SNPs that were significantly associated with SLE. The GWAS signals exhibited notable enrichment in m<sup>6</sup>A-SNPs and m<sup>7</sup>G-SNPs. These RNAm-SNPs showed both eQTL and pQTL effects. In our single-cell analysis, 16 RNAm-SNPs exhibited associations with gene expression levels across 13 distinct cell types, including <i>HLA-A, HLA-B, HLA-C, HLA-DQA1, HLA-DQB1, HLA-DRB1</i> and <i>IRF7</i>. We identified 58 noteworthy associations between the expression levels of 20 genes and SLE across 12 distinct immune cell types. Notably, <i>HLA-DQB1, HLA-DRB1</i> and <i>IRF7</i> exhibited abnormalities in CD8+ T cells, <i>IRF7</i> displayed abnormal expression in CD4+ T cells, while <i>HLA-DRB1</i> and <i>IRF7</i> were also distinctly perturbed in natural killer cells.</p><p><strong>Discussion: </strong>This study advances our understanding of the genetic basis of SLE by highlighting the significance of RNAm-SNPs and immune cell gene expression in SLE.</p>","PeriodicalId":13387,"journal":{"name":"Immunological Investigations","volume":" ","pages":"1264-1278"},"PeriodicalIF":2.9000,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Immunological Investigations","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1080/08820139.2024.2399577","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2024/9/4 0:00:00","PubModel":"Epub","JCR":"Q3","JCRName":"IMMUNOLOGY","Score":null,"Total":0}
引用次数: 0

Abstract

Introduction: This study aimed to elucidate the functional genes associated with systemic lupus erythematosus (SLE) in various cell types through the utilization of RNAm-SNPs.

Methods: Utilizing large-scale genetic data, we identified associations between RNAm-SNPs and SLE. The association between RNAm-SNPs and bulk and single-cell mRNA expression (eQTL) and protein levels (pQTL) were examined. Mendelian randomization and differential expression analyses were conducted to explore the links between gene expression, protein levels, and SLE.

Results: We identified 41 RNAm-SNPs that were significantly associated with SLE. The GWAS signals exhibited notable enrichment in m6A-SNPs and m7G-SNPs. These RNAm-SNPs showed both eQTL and pQTL effects. In our single-cell analysis, 16 RNAm-SNPs exhibited associations with gene expression levels across 13 distinct cell types, including HLA-A, HLA-B, HLA-C, HLA-DQA1, HLA-DQB1, HLA-DRB1 and IRF7. We identified 58 noteworthy associations between the expression levels of 20 genes and SLE across 12 distinct immune cell types. Notably, HLA-DQB1, HLA-DRB1 and IRF7 exhibited abnormalities in CD8+ T cells, IRF7 displayed abnormal expression in CD4+ T cells, while HLA-DRB1 and IRF7 were also distinctly perturbed in natural killer cells.

Discussion: This study advances our understanding of the genetic basis of SLE by highlighting the significance of RNAm-SNPs and immune cell gene expression in SLE.

查看原文
分享 分享
微信好友 朋友圈 QQ好友 复制链接
本刊更多论文
通过分析与 RNA 修饰相关的 SNPs,在全基因组范围内鉴定细胞类型特异的系统性红斑狼疮易感基因。
简介:本研究旨在通过利用RNAm-SNPs阐明与系统性红斑狼疮(SLE)相关的各种细胞类型的功能基因:本研究旨在通过利用RNAm-SNPs,在各种细胞类型中阐明与系统性红斑狼疮(SLE)相关的功能基因:利用大规模遗传数据,我们确定了RNAm-SNPs与系统性红斑狼疮之间的关联。我们研究了RNAm-SNPs与大量和单细胞mRNA表达(eQTL)和蛋白质水平(pQTL)之间的关联。我们还进行了孟德尔随机化和差异表达分析,以探讨基因表达、蛋白质水平与系统性红斑狼疮之间的联系:结果:我们发现了 41 个与系统性红斑狼疮显著相关的 RNAm-SNPs。GWAS信号在m6A-SNPs和m7G-SNPs中表现出明显的富集。这些RNAm-SNPs表现出eQTL和pQTL效应。在我们的单细胞分析中,16 个 RNAm-SNPs 与 13 种不同细胞类型的基因表达水平有关联,包括 HLA-A、HLA-B、HLA-C、HLA-DQA1、HLA-DQB1、HLA-DRB1 和 IRF7。我们在 12 种不同的免疫细胞类型中发现了 20 个基因的表达水平与系统性红斑狼疮之间存在 58 种值得注意的关联。值得注意的是,HLA-DQB1、HLA-DRB1和IRF7在CD8+ T细胞中表现异常,IRF7在CD4+ T细胞中表现异常,而HLA-DRB1和IRF7在自然杀伤细胞中也明显受到干扰:本研究强调了 RNAm-SNPs 和免疫细胞基因表达在系统性红斑狼疮中的重要性,从而加深了我们对系统性红斑狼疮遗传基础的理解。
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 去求助
来源期刊
Immunological Investigations
Immunological Investigations 医学-免疫学
CiteScore
5.50
自引率
7.10%
发文量
49
审稿时长
3 months
期刊介绍: Disseminating immunological developments on a worldwide basis, Immunological Investigations encompasses all facets of fundamental and applied immunology, including immunohematology and the study of allergies. This journal provides information presented in the form of original research articles and book reviews, giving a truly in-depth examination of the latest advances in molecular and cellular immunology.
期刊最新文献
Differential Expression of Granulysin, MHC Class I-Related Chain A, and Perforin in Serum and Peritoneal Fluid: Immune Dysregulation in Endometriosis-Related Infertility. Serum-Derived Exosomal TBX2-AS1 Exacerbates COPD by Altering the M1/M2 Ratio of Macrophages through Regulating the miR-423-5p/miR-23b-3p Axis. Evaluation of the Immunoadjuvant Effects of miR-155-Chitosan Polyplex on Leishmania major Infected Mice. Combination Effect of Radiotherapy and Targeted Therapy with NK Cell-Based Immunotherapy in head and Neck Squamous Cell Carcinoma. NOD1 Agonist Induces Proliferation and Plasma Cell Differentiation of Mouse B Cells Especially CD23high B Cells.
×
引用
GB/T 7714-2015
复制
MLA
复制
APA
复制
导出至
BibTeX EndNote RefMan NoteFirst NoteExpress
×
×
提示
您的信息不完整,为了账户安全,请先补充。
现在去补充
×
提示
您因"违规操作"
具体请查看互助需知
我知道了
×
提示
现在去查看 取消
×
提示
确定
0
微信
客服QQ
Book学术公众号 扫码关注我们
反馈
×
意见反馈
请填写您的意见或建议
请填写您的手机或邮箱
已复制链接
已复制链接
快去分享给好友吧!
我知道了
×
扫码分享
扫码分享
Book学术官方微信
Book学术文献互助
Book学术文献互助群
群 号:481959085
Book学术
文献互助 智能选刊 最新文献 互助须知 联系我们:info@booksci.cn
Book学术提供免费学术资源搜索服务,方便国内外学者检索中英文文献。致力于提供最便捷和优质的服务体验。
Copyright © 2023 Book学术 All rights reserved.
ghs 京公网安备 11010802042870号 京ICP备2023020795号-1