Integrating chromatin accessibility and GWAS identifies RUNX3 and TRAF1 as susceptibility genes for rheumatoid arthritis

Clicks: 19
ID: 317091
2026
Free PDF
Article Quality & Performance Metrics
Overall Quality
Not rated
Combines reader engagement with the AI quality analysis. This article has not been analysed, so there is no overall score — reader engagement is measured and shown alongside.
AI Quality Assessment
Not analyzed
Readership in this journal
Steady

Ranked #123 of 143 articles by views in journal of bone and mineral research : the official journal of the american society for bone and mineral research

Most read Least read

Bar heights use a square-root scale. Only the 120 most-read articles are drawn; the journal has 143 in total.

Mint this article as an NFT
Not yet minted

Create a permanent, verifiable on-chain record of this article on the Scimatic Network. The NFT is held in your Journament account, and you can withdraw it to your own wallet at any time.

5 SUSD one-off · no wallet required
Sign in to mint
Abstract
Genome-wide association studies (GWAS) have identified numerous rheumatoid arthritis (RA) associated genetic variants, most of which localize to non-coding regulatory regions (eg, enhancers), but their functional annotation remains a barrier to translating GWAS findings into mechanistic insights. This study hypothesized that these enhancer single nucleotide polymorphisms (SNPs) reside in the accessible chromatin domains of RA's target tissue (synovium) and modulate target gene expression by altering transcription factor (TF) binding affinity. Thus, leveraging prospectively collected RA synovial tissues, it aimed to identify key regulatory TFs and their roles in RA pathogenesis. The study integrated assay for transposase-accessible chromatin sequencing (ATAC-seq) data from synovial tissues of 7 RA patients with GWAS-derived RA-associated enhancer SNPs to prioritize TFs that bind these enhancers, with functional validation performed using primary fibroblast-like synoviocytes (FLSs) from RA synovial tissues and MH7A cell lines. Results showed that 1006 GWAS SNPs localized to enhancer regions and were significantly enriched in the open chromatin domains of RA synovium; TF enrichment analysis identified RUNX3 as the top candidate TF, which regulates FLS migration and invasion. Mechanistically, the G allele of rs1930785 binds RUNX3 in an allele-specific manner, upregulating the expression of its target gene TRAF1, which in turn exerts a protective effect on FLS homeostasis. The study confirms RUNX3 as a key TF regulating the activity of RA-associated enhancers, highlights the value of patient-derived synovial tissue data and the dual validation system, and lays a foundation for mechanistic research and targeted therapy for RA.
Reference Key
openalex_W7164302240 Use this key to autocite in the manuscript while using SciMatic Manuscript Manager or Thesis Manager
Authors Naining Wang, Dong‐Li Zhu, Feng Jiang, Yan Zhang, M H Li, Dajin Zhang, Shan-Shan Dong, Liqiang Zhi, Tie-Lin Yang, Shibin Hu, Yan Guo
Are you one of these authors? Claim your profile
Journal journal of bone and mineral research : the official journal of the american society for bone and mineral research
Year 2026
DOI
10.1093/jbmr/zjag098
URL
https://doi.org/10.1093/jbmr/zjag098
Keywords Keywords not found

Citations

No citations found. To add a citation, contact the admin at info@scimatic.org

Comments

No comments yet. Be the first to comment on this article.