Molecular crosstalk and potential causal mechanisms of rheumatoid arthritis and sarcopenia co-morbidity: A gene integration analysis

IF 3.9
Qiang Ren , Kaixi Ding , Wei Jiang , Wen Zhu , Yongxiang Gao
{"title":"Molecular crosstalk and potential causal mechanisms of rheumatoid arthritis and sarcopenia co-morbidity: A gene integration analysis","authors":"Qiang Ren ,&nbsp;Kaixi Ding ,&nbsp;Wei Jiang ,&nbsp;Wen Zhu ,&nbsp;Yongxiang Gao","doi":"10.1016/j.exger.2025.112729","DOIUrl":null,"url":null,"abstract":"<div><h3>Introduction</h3><div>Rheumatoid arthritis (RA) promotes the onset and progression of sarcopenia, yet mechanisms of co-morbidity between RA and sarcopenia are under-explored. Therefore, this study integrated Gene Expression Omnibus (GEO) and Genome-wide association studies (GWAS) data to comprehensively identify shared genes, associated mechanisms, and biological pathways in RA and sarcopenia.</div></div><div><h3>Methods</h3><div>Utilizing two GEO datasets—GSE226151, which includes 60 RNA-seq samples of skeletal muscle from healthy aged, pre-sarcopenia, and sarcopenia individuals, and GSE55235, with 20 RNA-seq samples of synovial tissue from healthy and RA joints—we performed differentially expressed genes analysis, weighted gene co-expression network analysis to identify crosstalk genes in RA and sarcopenia, and enrichment analysis for these genes. Using relevant GWAS datasets, SMR analyses and cis-eQTL analyses were performed. We further validated and identified key crosstalk genes and explored potential causal associations between key crosstalk genes and RA and sarcopenia-related traits.</div></div><div><h3>Results</h3><div>We identified 25 crosstalk genes shared between RA and sarcopenia, which are involved in immune-inflammatory response pathways, including neutrophil extracellular trap formation and Fc gamma receptor-mediated phagocytosis. SMR analysis further identified six core crosstalk genes: NCF1, FCGR2A, FCGR3A, SORL1, FCGR3B, and ITGAX (<em>P</em><sub><em>SMR</em></sub> &lt; 0.05). <em>cis</em>-eQTL analysis showed that FCGR2A might have a negative causal association with appendicular lean mass, whole body fat-free mass, and a positive causal association with RA (<em>P</em> &lt; 0.05).</div></div><div><h3>Conclusion</h3><div>Overall, this study is the first to reveal the molecular crosstalk between RA and sarcopenia, identifying 25 shared genes and key immune-inflammatory response-related pathways. Further SMR and cis-eQTL analyses were conducted to validate six core genes, with FCGR2A emerging as a potential drug target for RA-associated sarcopenia. These findings provide new insights into the comorbid mechanisms of RA and sarcopenia, offering potential therapeutic targets for both conditions.</div></div>","PeriodicalId":94003,"journal":{"name":"Experimental gerontology","volume":"203 ","pages":"Article 112729"},"PeriodicalIF":3.9000,"publicationDate":"2025-03-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Experimental gerontology","FirstCategoryId":"1085","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S0531556525000580","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"","JCRName":"","Score":null,"Total":0}
引用次数: 0

Abstract

Introduction

Rheumatoid arthritis (RA) promotes the onset and progression of sarcopenia, yet mechanisms of co-morbidity between RA and sarcopenia are under-explored. Therefore, this study integrated Gene Expression Omnibus (GEO) and Genome-wide association studies (GWAS) data to comprehensively identify shared genes, associated mechanisms, and biological pathways in RA and sarcopenia.

Methods

Utilizing two GEO datasets—GSE226151, which includes 60 RNA-seq samples of skeletal muscle from healthy aged, pre-sarcopenia, and sarcopenia individuals, and GSE55235, with 20 RNA-seq samples of synovial tissue from healthy and RA joints—we performed differentially expressed genes analysis, weighted gene co-expression network analysis to identify crosstalk genes in RA and sarcopenia, and enrichment analysis for these genes. Using relevant GWAS datasets, SMR analyses and cis-eQTL analyses were performed. We further validated and identified key crosstalk genes and explored potential causal associations between key crosstalk genes and RA and sarcopenia-related traits.

Results

We identified 25 crosstalk genes shared between RA and sarcopenia, which are involved in immune-inflammatory response pathways, including neutrophil extracellular trap formation and Fc gamma receptor-mediated phagocytosis. SMR analysis further identified six core crosstalk genes: NCF1, FCGR2A, FCGR3A, SORL1, FCGR3B, and ITGAX (PSMR < 0.05). cis-eQTL analysis showed that FCGR2A might have a negative causal association with appendicular lean mass, whole body fat-free mass, and a positive causal association with RA (P < 0.05).

Conclusion

Overall, this study is the first to reveal the molecular crosstalk between RA and sarcopenia, identifying 25 shared genes and key immune-inflammatory response-related pathways. Further SMR and cis-eQTL analyses were conducted to validate six core genes, with FCGR2A emerging as a potential drug target for RA-associated sarcopenia. These findings provide new insights into the comorbid mechanisms of RA and sarcopenia, offering potential therapeutic targets for both conditions.
求助全文
约1分钟内获得全文 求助全文
来源期刊
Experimental gerontology
Experimental gerontology Ageing, Biochemistry, Geriatrics and Gerontology
CiteScore
6.70
自引率
0.00%
发文量
0
审稿时长
66 days
×
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
确定
请完成安全验证×
copy
已复制链接
快去分享给好友吧!
我知道了
右上角分享
点击右上角分享
0
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 布克学术 All rights reserved.
京ICP备2023020795号-1
ghs 京公网安备 11010802042870号
Book学术文献互助
Book学术文献互助群
群 号:481959085
Book学术官方微信