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A landscape of gene expression regulation for synovium in arthritis

Author

Listed:
  • Feng Jiang

    (Xi’an Jiaotong University)

  • Shou-Ye Hu

    (Xi’an Jiaotong University)

  • Wen Tian

    (Xi’an Jiaotong University)

  • Nai-Ning Wang

    (Xi’an Jiaotong University)

  • Ning Yang

    (Xi’an Jiaotong University)

  • Shan-Shan Dong

    (Xi’an Jiaotong University)

  • Hui-Miao Song

    (Xi’an Jiaotong University)

  • Da-Jin Zhang

    (Xi’an Jiaotong University)

  • Hui-Wu Gao

    (Xi’an Jiaotong University)

  • Chen Wang

    (Xi’an Jiaotong University)

  • Hao Wu

    (Xi’an Jiaotong University)

  • Chang-Yi He

    (Xi’an Jiaotong University)

  • Dong-Li Zhu

    (Xi’an Jiaotong University)

  • Xiao-Feng Chen

    (Xi’an Jiaotong University)

  • Yan Guo

    (Xi’an Jiaotong University)

  • Zhi Yang

    (Xi’an Jiaotong University)

  • Tie-Lin Yang

    (Xi’an Jiaotong University)

Abstract

The synovium is an important component of any synovial joint and is the major target tissue of inflammatory arthritis. However, the multi-omics landscape of synovium required for functional inference is absent from large-scale resources. Here we integrate genomics with transcriptomics and chromatin accessibility features of human synovium in up to 245 arthritic patients, to characterize the landscape of genetic regulation on gene expression and the regulatory mechanisms mediating arthritic diseases predisposition. We identify 4765 independent primary and 616 secondary cis-expression quantitative trait loci (cis-eQTLs) in the synovium and find that the eQTLs with multiple independent signals have stronger effects and heritability than single independent eQTLs. Integration of genome-wide association studies (GWASs) and eQTLs identifies 84 arthritis related genes, revealing 38 novel genes which have not been reported by previous studies using eQTL data from the GTEx project or immune cells. We further develop a method called eQTac to identify variants that could affect gene expression by affecting chromatin accessibility and identify 1517 regions with potential regulatory function of chromatin accessibility. Altogether, our study provides a comprehensive synovium multi-omics resource for arthritic diseases and gains new insights into the regulation of gene expression.

Suggested Citation

  • Feng Jiang & Shou-Ye Hu & Wen Tian & Nai-Ning Wang & Ning Yang & Shan-Shan Dong & Hui-Miao Song & Da-Jin Zhang & Hui-Wu Gao & Chen Wang & Hao Wu & Chang-Yi He & Dong-Li Zhu & Xiao-Feng Chen & Yan Guo , 2024. "A landscape of gene expression regulation for synovium in arthritis," Nature Communications, Nature, vol. 15(1), pages 1-16, December.
    • Handle: RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-024-45652-x
    DOI: 10.1038/s41467-024-45652-x
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