ArticleFrontiers in immunology2024
Genetic associations in ankylosing spondylitis: circulating proteins as drug targets and biomarkers.
Article in Frontiers in immunology, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.
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Who cites it
10 citing papers in PubMed.
- Integrating multi-omics and mendelian randomization identifies therapeutic targets for Lichen Sclerosus: A druggable genome-wide study.Global medical genetics · 2026Article
- ACSS2-KAT5 complex-driven histone crotonylation orchestrates a pro-inflammatory program to promote the transition from MASLD to MASH.Nature communications · 2026Article
- OptiSyn: an interpretable, multi-omics-driven graph convolutional network framework for synergy-oriented drug combination design in disease treatment.Chinese medicine · 2026Article
- Gut microbiota and ankylosing spondylitis: mechanisms, functional pathways, and research trends.Frontiers in microbiology · 2026Article
- Exploration of potential novel drug targets for rheumatoid arthritis by plasma proteome screening.PLoS computational biology · 2025Article
- Exploring the genetic components and multi-omics sources of inflammatory bowel disease from the perspective of autoimmune disorders.Clinical rheumatology · 2025Article
- Proteomics signatures associated with hip arthropathy in ankylosing spondylitis.Frontiers in medicine · 2025Article
- Gut microbiota and ankylosing spondylitis: current insights and future challenges.Microbial cell (Graz, Austria) · 2025Review
- A Multitrait Analysis of Genome-Wide Association Study Reveals the Shared Genetic Architecture Between Inflammatory Bowel Disease and Ankylosing Spondylitis.Mediators of inflammation · 2025Article
- From advanced imaging to molecular insights: the state of the art in omics for axial spondyloarthritis.Therapeutic advances in musculoskeletal disease · 2025Review
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4 authors.
Funding
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Abstract
Background: Ankylosing spondylitis (AS) is a complex condition with a significant genetic component. This study explored circulating proteins as potential genetic drug targets or biomarkers to prevent AS, addressing the need for innovative and safe treatments. Methods: We analyzed extensive data from protein quantitative trait loci (pQTLs) with up to 1,949 instrumental variables (IVs) and selected the top single-nucleotide polymorphism (SNP) associated with AS risk. Utilizing a two-sample Mendelian randomization (MR) approach, we assessed the causal relationships between identified proteins and AS risk. Colocalization analysis, functional enrichment, and construction of protein-protein interaction networks further supported these findings. We utilized phenome-wide MR (phenMR) analysis for broader validation and repurposing of drugs targeting these proteins. The Drug-Gene Interaction database (DGIdb) was employed to corroborate drug associations with potential therapeutic targets. Additionally, molecular docking (MD) techniques were applied to evaluate the interaction between target protein and four potential AS drugs identified from the DGIdb. Results: Our analysis identified 1,654 plasma proteins linked to AS, with 868 up-regulated and 786 down-regulated. 18 proteins (AGER, AIF1, ATF6B, C4A, CFB, CLIC1, COL11A2, ERAP1, HLA-DQA2, HSPA1L, IL23R, LILRB3, MAPK14, MICA, MICB, MPIG6B, TNXB, and VARS1) that show promise as therapeutic targets for AS or biomarkers, especially MAPK14, supported by evidence of colocalization. PhenMR analysis linked these proteins to AS and other diseases, while DGIdb analysis identified potential drugs related to MAPK14. MD analysis indicated strong binding affinities between MAPK14 and four potential AS drugs, suggesting effective target-drug interactions. Conclusion: This study underscores the utility of MR analysis in AS research for identifying biomarkers and therapeutic drug targets. The involvement of Th17 cell differentiation-related proteins in AS pathogenesis is particularly notable. Clinical validation and further investigation are essential for future applications.
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