IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v15y2024i1d10.1038_s41467-024-45652-x.html
   My bibliography  Save this article

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
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/s41467-024-45652-x
    File Function: Abstract
    Download Restriction: no
    File URL: https://libkey.io/10.1038/s41467-024-45652-x?utm_source=ideas
    LibKey link: if access is restricted and if your library uses this service, LibKey will redirect you to where you can use your library subscription to access this item
    ---><---

    References listed on IDEAS

    as
    1. Chris Wallace, 2021. "A more accurate method for colocalisation analysis allowing for multiple causal variants," PLOS Genetics, Public Library of Science, vol. 17(9), pages 1-11, September.
    2. Yukinori Okada & Di Wu & Gosia Trynka & Towfique Raj & Chikashi Terao & Katsunori Ikari & Yuta Kochi & Koichiro Ohmura & Akari Suzuki & Shinji Yoshida & Robert R. Graham & Arun Manoharan & Ward Ortman, 2014. "Genetics of rheumatoid arthritis contributes to biology and drug discovery," Nature, Nature, vol. 506(7488), pages 376-381, February.
    3. Jessica Zuin & Gregory Roth & Yinxiu Zhan & Julie Cramard & Josef Redolfi & Ewa Piskadlo & Pia Mach & Mariya Kryzhanovska & Gergely Tihanyi & Hubertus Kohler & Mathias Eder & Christ Leemans & Bas Stee, 2022. "Nonlinear control of transcription through enhancer–promoter interactions," Nature, Nature, vol. 604(7906), pages 571-577, April.
    4. Mahmoud Ghandi & Dongwon Lee & Morteza Mohammad-Noori & Michael A Beer, 2014. "Enhanced Regulatory Sequence Prediction Using Gapped k-mer Features," PLOS Computational Biology, Public Library of Science, vol. 10(7), pages 1-15, July.
    5. Monkol Lek & Konrad J. Karczewski & Eric V. Minikel & Kaitlin E. Samocha & Eric Banks & Timothy Fennell & Anne H. O’Donnell-Luria & James S. Ware & Andrew J. Hill & Beryl B. Cummings & Taru Tukiainen , 2016. "Analysis of protein-coding genetic variation in 60,706 humans," Nature, Nature, vol. 536(7616), pages 285-291, August.
    6. Julia Steinberg & Lorraine Southam & Theodoros I. Roumeliotis & Matthew J. Clark & Raveen L. Jayasuriya & Diane Swift & Karan M. Shah & Natalie C. Butterfield & Roger A. Brooks & Andrew W. McCaskie & , 2021. "A molecular quantitative trait locus map for osteoarthritis," Nature Communications, Nature, vol. 12(1), pages 1-11, December.
    7. Carles A. Boix & Benjamin T. James & Yongjin P. Park & Wouter Meuleman & Manolis Kellis, 2021. "Regulatory genomic circuitry of human disease loci by integrative epigenomics," Nature, Nature, vol. 590(7845), pages 300-307, February.
    Full references (including those not matched with items on IDEAS)

    Most related items

    These are the items that most often cite the same works as this one and are cited by the same works as this one.
    1. Sophie A. Riesmeijer & Zoha Kamali & Michael Ng & Dmitriy Drichel & Bram Piersma & Kerstin Becker & Thomas B. Layton & Jagdeep Nanchahal & Michael Nothnagel & Ahmad Vaez & Hans Christian Hennies & Pau, 2024. "A genome-wide association meta-analysis implicates Hedgehog and Notch signaling in Dupuytren’s disease," Nature Communications, Nature, vol. 15(1), pages 1-11, December.
    2. Heng Du & Lei Zhou & Zhen Liu & Yue Zhuo & Meilin Zhang & Qianqian Huang & Shiyu Lu & Kai Xing & Li Jiang & Jian-Feng Liu, 2024. "The 1000 Chinese Indigenous Pig Genomes Project provides insights into the genomic architecture of pigs," Nature Communications, Nature, vol. 15(1), pages 1-18, December.
    3. Gökberk Alagöz & Else Eising & Yasmina Mekki & Giacomo Bignardi & Pierre Fontanillas & Michel G. Nivard & Michelle Luciano & Nancy J. Cox & Simon E. Fisher & Reyna L. Gordon, 2025. "The shared genetic architecture and evolution of human language and musical rhythm," Nature Human Behaviour, Nature, vol. 9(2), pages 376-390, February.
    4. Evelyn Kabirova & Anastasiya Ryzhkova & Varvara Lukyanchikova & Anna Khabarova & Alexey Korablev & Tatyana Shnaider & Miroslav Nuriddinov & Polina Belokopytova & Alexander Smirnov & Nikita V. Khotskin, 2024. "TAD border deletion at the Kit locus causes tissue-specific ectopic activation of a neighboring gene," Nature Communications, Nature, vol. 15(1), pages 1-16, December.
    5. Jujiao Kang & Yue-Ting Deng & Bang-Sheng Wu & Wei-Shi Liu & Ze-Yu Li & Shitong Xiang & Liu Yang & Jia You & Xiaohong Gong & Tianye Jia & Jin-Tai Yu & Wei Cheng & Jianfeng Feng, 2024. "Whole exome sequencing analysis identifies genes for alcohol consumption," Nature Communications, Nature, vol. 15(1), pages 1-15, December.
    6. Pietro Demela & Nicola Pirastu & Blagoje Soskic, 2023. "Cross-disorder genetic analysis of immune diseases reveals distinct gene associations that converge on common pathways," Nature Communications, Nature, vol. 14(1), pages 1-12, December.
    7. Samuel S. Kim & Buu Truong & Karthik Jagadeesh & Kushal K. Dey & Amber Z. Shen & Soumya Raychaudhuri & Manolis Kellis & Alkes L. Price, 2024. "Leveraging single-cell ATAC-seq and RNA-seq to identify disease-critical fetal and adult brain cell types," Nature Communications, Nature, vol. 15(1), pages 1-11, December.
    8. Hossein Salari & Geneviève Fourel & Daniel Jost, 2024. "Transcription regulates the spatio-temporal dynamics of genes through micro-compartmentalization," Nature Communications, Nature, vol. 15(1), pages 1-15, December.
    9. Eun Seop Seo & Ji Won Lee & Jinyeong Lim & Sunghwan Shin & Hee Won Cho & Hee Young Ju & Keon Hee Yoo & Ki Woong Sung & Woong-Yang Park, 2024. "Germline functional variants contribute to somatic mutation and outcomes in neuroblastoma," Nature Communications, Nature, vol. 15(1), pages 1-12, December.
    10. Ruoyu Tian & Tian Ge & Hyeokmoon Kweon & Daniel B. Rocha & Max Lam & Jimmy Z. Liu & Kritika Singh & Daniel F. Levey & Joel Gelernter & Murray B. Stein & Ellen A. Tsai & Hailiang Huang & Christopher F., 2024. "Whole-exome sequencing in UK Biobank reveals rare genetic architecture for depression," Nature Communications, Nature, vol. 15(1), pages 1-12, December.
    11. Mary-Ellen Lynall & Blagoje Soskic & James Hayhurst & Jeremy Schwartzentruber & Daniel F. Levey & Gita A. Pathak & Renato Polimanti & Joel Gelernter & Murray B. Stein & Gosia Trynka & Menna R. Clatwor, 2022. "Genetic variants associated with psychiatric disorders are enriched at epigenetically active sites in lymphoid cells," Nature Communications, Nature, vol. 13(1), pages 1-15, December.
    12. Birgit Burkhardt & Ulf Michgehl & Jonas Rohde & Tabea Erdmann & Philipp Berning & Katrin Reutter & Marius Rohde & Arndt Borkhardt & Thomas Burmeister & Sandeep Dave & Alexandar Tzankov & Martin Dugas , 2022. "Clinical relevance of molecular characteristics in Burkitt lymphoma differs according to age," Nature Communications, Nature, vol. 13(1), pages 1-12, December.
    13. Seong Kyu Han & Michelle T. McNulty & Christopher J. Benway & Pei Wen & Anya Greenberg & Ana C. Onuchic-Whitford & Dongkeun Jang & Jason Flannick & Noël P. Burtt & Parker C. Wilson & Benjamin D. Humph, 2023. "Mapping genomic regulation of kidney disease and traits through high-resolution and interpretable eQTLs," Nature Communications, Nature, vol. 14(1), pages 1-16, December.
    14. Maria Stahl Madsen & Marjoleine F. Broekema & Martin Rønn Madsen & Arjen Koppen & Anouska Borgman & Cathrin Gräwe & Elisabeth G. K. Thomsen & Denise Westland & Mariette E. G. Kranendonk & Marian Groot, 2022. "PPARγ lipodystrophy mutants reveal intermolecular interactions required for enhancer activation," Nature Communications, Nature, vol. 13(1), pages 1-19, December.
    15. Mark W. Youngblood & Zeynep Erson-Omay & Chang Li & Hinda Najem & Süleyman Coșkun & Evgeniya Tyrtova & Julio D. Montejo & Danielle F. Miyagishima & Tanyeri Barak & Sayoko Nishimura & Akdes Serin Harma, 2023. "Super-enhancer hijacking drives ectopic expression of hedgehog pathway ligands in meningiomas," Nature Communications, Nature, vol. 14(1), pages 1-16, December.
    16. James T. Topham & Erica S. Tsang & Joanna M. Karasinska & Andrew Metcalfe & Hassan Ali & Steve E. Kalloger & Veronika Csizmok & Laura M. Williamson & Emma Titmuss & Karina Nielsen & Gian Luca Negri & , 2022. "Integrative analysis of KRAS wildtype metastatic pancreatic ductal adenocarcinoma reveals mutation and expression-based similarities to cholangiocarcinoma," Nature Communications, Nature, vol. 13(1), pages 1-13, December.
    17. Duc-Hau Le, 2021. "A network-based method for predicting disease-associated enhancers," PLOS ONE, Public Library of Science, vol. 16(12), pages 1-20, December.
    18. Zhangyuan Pan & Yuelin Yao & Hongwei Yin & Zexi Cai & Ying Wang & Lijing Bai & Colin Kern & Michelle Halstead & Ganrea Chanthavixay & Nares Trakooljul & Klaus Wimmers & Goutam Sahana & Guosheng Su & M, 2021. "Pig genome functional annotation enhances the biological interpretation of complex traits and human disease," Nature Communications, Nature, vol. 12(1), pages 1-15, December.
    19. Pingting Ying & Can Chen & Zequn Lu & Shuoni Chen & Ming Zhang & Yimin Cai & Fuwei Zhang & Jinyu Huang & Linyun Fan & Caibo Ning & Yanmin Li & Wenzhuo Wang & Hui Geng & Yizhuo Liu & Wen Tian & Zhiyong, 2023. "Genome-wide enhancer-gene regulatory maps link causal variants to target genes underlying human cancer risk," Nature Communications, Nature, vol. 14(1), pages 1-20, December.
    20. Laureano Tomás-Daza & Llorenç Rovirosa & Paula López-Martí & Andrea Nieto-Aliseda & François Serra & Ainoa Planas-Riverola & Oscar Molina & Rebecca McDonald & Cedric Ghevaert & Esther Cuatrecasas & Do, 2023. "Low input capture Hi-C (liCHi-C) identifies promoter-enhancer interactions at high-resolution," Nature Communications, Nature, vol. 14(1), pages 1-16, December.

    More about this item

    Statistics

    Access and download statistics

    Corrections

    All material on this site has been provided by the respective publishers and authors. You can help correct errors and omissions. When requesting a correction, please mention this item's handle: RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-024-45652-x. See general information about how to correct material in RePEc.

    If you have authored this item and are not yet registered with RePEc, we encourage you to do it here. This allows to link your profile to this item. It also allows you to accept potential citations to this item that we are uncertain about.

    If CitEc recognized a bibliographic reference but did not link an item in RePEc to it, you can help with this form .

    If you know of missing items citing this one, you can help us creating those links by adding the relevant references in the same way as above, for each refering item. If you are a registered author of this item, you may also want to check the "citations" tab in your RePEc Author Service profile, as there may be some citations waiting for confirmation.

    For technical questions regarding this item, or to correct its authors, title, abstract, bibliographic or download information, contact: Sonal Shukla or Springer Nature Abstracting and Indexing (email available below). General contact details of provider: http://www.nature.com .

    Please note that corrections may take a couple of weeks to filter through the various RePEc services.

    IDEAS is a RePEc service. RePEc uses bibliographic data supplied by the respective publishers.