Multi-layered functional genomics prioritizes candidate effectors and regulatory mechanisms of ankylosing spondylitis - Report - MDSpire

Multi-layered functional genomics prioritizes candidate effectors and regulatory mechanisms of ankylosing spondylitis

  • By

  • Fanyu Meng

  • Ling Chen

  • Meng Li

  • Qingqing Zhang

  • Peiying Wang

  • Ruifeng Lin

  • Jiani Liu

  • Zhao Yuan

  • Kexin Chen

  • Zhaoxia Li

  • Yetong Xie

  • Abuduwahapu Aierken

  • Furkat Yalkun

  • Chulan Li

  • Yuan Ma

  • Jianhui Chen

  • Ziwen Xu

  • Fei Zhong

  • June 1, 2026

  • 0 min

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Clinical Report: Prioritization of Candidate Effectors in Ankylosing Spondylitis

Overview

This study identifies 30 genome-wide significant loci associated with ankylosing spondylitis (AS) through a meta-analysis of over 7,500 cases. It prioritizes 64 causal-candidate genes and highlights the need for further experimental validation of these findings.

Background

Ankylosing spondylitis is a chronic inflammatory disease with a high heritability rate, yet the genetic factors contributing to its pathogenesis remain largely undefined. Understanding the genetic architecture beyond the HLA-B*27 association is crucial for developing targeted therapies and improving patient outcomes. This study employs advanced genomic techniques to elucidate the underlying mechanisms of AS.

Data Highlights

MetricValue
Genome-wide significant loci30
Significant variants26,178
Lambda GC1.09
LDSC intercept1.045 (SE = 0.009)
Attenuation ratio0.365 (SE = 0.075)

Key Findings

  • Identified 30 genome-wide significant loci associated with AS.
  • Prioritized 64 causal-candidate genes with a posterior inclusion probability > 0.5.
  • Gene expression accounted for 19.5% of AS heritability.
  • Seven genes showed convergent evidence from cTWAS and colocalization.
  • Cross-trait LDSC revealed positive genetic correlations with inflammatory bowel disease and psoriasis.
  • Functional studies indicated TBKBP1 and XCL1 as significant in Jurkat T cells.

Clinical Implications

The findings underscore the importance of integrating genomic data to identify potential therapeutic targets in AS. Clinicians should consider these candidate genes in future research and therapeutic strategies, as they may inform personalized treatment approaches.

Conclusion

This study enhances our understanding of the genetic landscape of ankylosing spondylitis and sets the stage for future experimental validation of identified candidate genes and regulatory pathways.

Related Resources & Content

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  2. The Journal of Infectious Diseases, 2023 -- Comprehensive Meta-Analysis of Host Responses to Staphylococcus aureus
  3. Clinical Rheumatology, 2024 -- Discovery and validation of inflammatory markers in primary Sjögren’s syndrome
  4. The 2025 British Society for Rheumatology guideline for the treatment of axial spondyloarthritis with biologic and targeted synthetic DMARDs - PMC
  5. ASAS consensus definition of early axial spondyloarthritis - ScienceDirect
  6. Clinical Rheumatology (Springer) — Identification of Th17-associated genes PGAP1 and TMBIM1 as promising biomarkers for diagnosis and prognosis in systemic sclerosis: Insights from bioinformatics and murine studies
  7. UCB announces U.S. FDA approvals for BIMZELX[®] for the treatment of psoriatic arthritis
  8. HLA-B27 and spondyloarthritis: at the crossroads of innate and adaptive immunity
  9. The 2025 British Society for Rheumatology guideline for the treatment of axial spondyloarthritis with biologic and targeted synthetic DMARDs - PMC
  10. ASAS consensus definition of early axial spondyloarthritis - ScienceDirect
  11. Exercise prescription for axial spondyloarthritis: a systematic review and meta-analysis of randomized controlled trials
  12. Efficacy and Safety of Interleukin-17 and Janus Kinase Inhibitors in Ankylosing Spondylitis: A Systematic Review and Network Meta-Analysis - PubMed
  13. Risk of new-onset and recurrent uveitis with different biologics for ankylosing spondylitis: a network meta-analysis - PubMed
  14. Identifying prioritization of therapeutic targets for ankylosing spondylitis: a multi-omics Mendelian randomization study - PubMed
  15. Dai et al. Journal of Translational Medicine (2024) 22:1115

Original Source(s)

Multi-layered functional genomics prioritizes candidate effectors and regulatory mechanisms of ankylosing spondylitis

  • by Fanyu Meng, Ling Chen, Meng Li, Qingqing Zhang, Peiying Wang, Ruifeng Lin, Jiani Liu, Zhao Yuan, Kexin Chen, Zhaoxia Li, Yetong Xie, Abuduwahapu Aierken, Furkat Yalkun, Chulan Li, Yuan Ma, Jianhui Chen, Ziwen Xu, Fei Zhong

  • June 1, 2026

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