IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v14y2023i1d10.1038_s41467-023-36678-8.html
   My bibliography  Save this article

Multitrait genome-wide analyses identify new susceptibility loci and candidate drugs to primary sclerosing cholangitis

Author

Listed:
  • Younghun Han

    (Baylor College of Medicine
    Baylor College of Medicine)

  • Jinyoung Byun

    (Baylor College of Medicine
    Baylor College of Medicine
    Baylor College of Medicine)

  • Catherine Zhu

    (Baylor College of Medicine)

  • Ryan Sun

    (University of Texas, M.D. Anderson Cancer Center)

  • Julia Y. Roh

    (Ochsner Health)

  • Heather J. Cordell

    (Newcastle University)

  • Hyun-Sung Lee

    (Baylor College of Medicine)

  • Vikram R. Shaw

    (Baylor College of Medicine)

  • Sung Wook Kang

    (Baylor College of Medicine)

  • Javad Razjouyan

    (Michael E. DeBakey VA Medical Center
    VA Office of Research and Development
    Baylor College of Medicine
    Michael E. DeBakey VA Medical Center)

  • Matthew A. Cooley

    (Mayo Clinic)

  • Manal M. Hassan

    (The University of Texas MD Anderson Cancer Center)

  • Katherine A. Siminovitch

    (University of Toronto
    Mount Sinai Hospital, Lunenfeld-Tanenbaum Research Institute and Toronto General Research Institute, Toronto)

  • Trine Folseraas

    (Oslo University Hospital Rikshospitalet)

  • David Ellinghaus

    (Christian-Albrechts-University of Kiel)

  • Annika Bergquist

    (Karolinska Institutet, Karolinska University Hospital)

  • Simon M. Rushbrook

    (Norfolk and Norwich University Hospital
    University of East Anglia)

  • Andre Franke

    (Christian-Albrechts-University of Kiel)

  • Tom H. Karlsen

    (Oslo University Hospital Rikshospitalet and University of Oslo)

  • Konstantinos N. Lazaridis

    (Mayo Clinic)

  • Katherine A. McGlynn

    (National Cancer Institute)

  • Lewis R. Roberts

    (Oslo University Hospital Rikshospitalet and University of Oslo)

  • Christopher I. Amos

    (Baylor College of Medicine
    Baylor College of Medicine
    Baylor College of Medicine)

Abstract

Primary sclerosing cholangitis (PSC) is a rare autoimmune bile duct disease that is strongly associated with immune-mediated disorders. In this study, we implemented multitrait joint analyses to genome-wide association summary statistics of PSC and numerous clinical and epidemiological traits to estimate the genetic contribution of each trait and genetic correlations between traits and to identify new lead PSC risk-associated loci. We identified seven new loci that have not been previously reported and one new independent lead variant in the previously reported locus. Functional annotation and fine-mapping nominated several potential susceptibility genes such as MANBA and IRF5. Network-based in silico drug efficacy screening provided candidate agents for further study of pharmacological effect in PSC.

Suggested Citation

  • Younghun Han & Jinyoung Byun & Catherine Zhu & Ryan Sun & Julia Y. Roh & Heather J. Cordell & Hyun-Sung Lee & Vikram R. Shaw & Sung Wook Kang & Javad Razjouyan & Matthew A. Cooley & Manal M. Hassan & , 2023. "Multitrait genome-wide analyses identify new susceptibility loci and candidate drugs to primary sclerosing cholangitis," Nature Communications, Nature, vol. 14(1), pages 1-13, December.
    • Handle: RePEc:nat:natcom:v:14:y:2023:i:1:d:10.1038_s41467-023-36678-8
    DOI: 10.1038/s41467-023-36678-8
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/s41467-023-36678-8
    File Function: Abstract
    Download Restriction: no
    File URL: https://libkey.io/10.1038/s41467-023-36678-8?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. Kyoko Watanabe & Erdogan Taskesen & Arjen Bochoven & Danielle Posthuma, 2017. "Functional mapping and annotation of genetic associations with FUMA," Nature Communications, Nature, vol. 8(1), pages 1-11, December.
    2. Carl D. Langefeld & Hannah C. Ainsworth & Deborah S. Cunninghame Graham & Jennifer A. Kelly & Mary E. Comeau & Miranda C. Marion & Timothy D. Howard & Paula S. Ramos & Jennifer A. Croker & David L. Mo, 2017. "Transancestral mapping and genetic load in systemic lupus erythematosus," Nature Communications, Nature, vol. 8(1), pages 1-18, December.
    3. Vincent L. Chen & Xiaomeng Du & Yanhua Chen & Annapurna Kuppa & Samuel K. Handelman & Rishel B. Vohnoutka & Patricia A. Peyser & Nicholette D. Palmer & Lawrence F. Bielak & Brian Halligan & Elizabeth , 2021. "Genome-wide association study of serum liver enzymes implicates diverse metabolic and liver pathology," Nature Communications, Nature, vol. 12(1), pages 1-13, December.
    4. Fang Qiu & Ruqi Tang & Xianbo Zuo & Xingjuan Shi & Yiran Wei & Xiaodong Zheng & Yaping Dai & Yuhua Gong & Lan Wang & Ping Xu & Xiang Zhu & Jian Wu & Chongxu Han & Yueqiu Gao & Kui Zhang & Yuzhang Jian, 2017. "A genome-wide association study identifies six novel risk loci for primary biliary cholangitis," Nature Communications, Nature, vol. 8(1), pages 1-8, April.
    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. Natalie DeForest & Yuqi Wang & Zhiyi Zhu & Jacqueline S. Dron & Ryan Koesterer & Pradeep Natarajan & Jason Flannick & Tiffany Amariuta & Gina M. Peloso & Amit R. Majithia, 2024. "Genome-wide discovery and integrative genomic characterization of insulin resistance loci using serum triglycerides to HDL-cholesterol ratio as a proxy," Nature Communications, Nature, vol. 15(1), pages 1-17, December.
    2. Bhuwan Khatri & Kandice L. Tessneer & Astrid Rasmussen & Farhang Aghakhanian & Tove Ragna Reksten & Adam Adler & Ilias Alevizos & Juan-Manuel Anaya & Lara A. Aqrawi & Eva Baecklund & Johan G. Brun & S, 2022. "Genome-wide association study identifies Sjögren’s risk loci with functional implications in immune and glandular cells," Nature Communications, Nature, vol. 13(1), pages 1-17, December.
    3. Danni A. Gadd & Robert F. Hillary & Daniel L. McCartney & Liu Shi & Aleks Stolicyn & Neil A. Robertson & Rosie M. Walker & Robert I. McGeachan & Archie Campbell & Shen Xueyi & Miruna C. Barbu & Claire, 2022. "Integrated methylome and phenome study of the circulating proteome reveals markers pertinent to brain health," Nature Communications, Nature, vol. 13(1), pages 1-14, December.
    4. Fasil Tekola-Ayele & Xuehuo Zeng & Suvo Chatterjee & Marion Ouidir & Corina Lesseur & Ke Hao & Jia Chen & Markos Tesfaye & Carmen J. Marsit & Tsegaselassie Workalemahu & Ronald Wapner, 2022. "Placental multi-omics integration identifies candidate functional genes for birthweight," Nature Communications, Nature, vol. 13(1), pages 1-12, December.
    5. Xingjie Hao & Zhonghe Shao & Ning Zhang & Minghui Jiang & Xi Cao & Si Li & Yunlong Guan & Chaolong Wang, 2023. "Integrative genome-wide analyses identify novel loci associated with kidney stones and provide insights into its genetic architecture," Nature Communications, Nature, vol. 14(1), pages 1-12, December.
    6. Wendiao Zhang & Ming Zhang & Zhenhong Xu & Hongye Yan & Huimin Wang & Jiamei Jiang & Juan Wan & Beisha Tang & Chunyu Liu & Chao Chen & Qingtuan Meng, 2023. "Human forebrain organoid-based multi-omics analyses of PCCB as a schizophrenia associated gene linked to GABAergic pathways," Nature Communications, Nature, vol. 14(1), pages 1-13, December.
    7. Isabelle Austin-Zimmerman & Daniel F. Levey & Olga Giannakopoulou & Joseph D. Deak & Marco Galimberti & Keyrun Adhikari & Hang Zhou & Spiros Denaxas & Haritz Irizar & Karoline Kuchenbaecker & Andrew M, 2023. "Genome-wide association studies and cross-population meta-analyses investigating short and long sleep duration," Nature Communications, Nature, vol. 14(1), pages 1-15, December.
    8. You Li & Zhiqiang Li & Ruiling Chen & Min Lian & Hanxiao Wang & Yiran Wei & Zhengrui You & Jun Zhang & Bo Li & Yikang Li & Bingyuan Huang & Yong Chen & Qiaoyan Liu & Zhuwan Lyu & Xueying Liang & Qi Mi, 2023. "A regulatory variant at 19p13.3 is associated with primary biliary cholangitis risk and ARID3A expression," Nature Communications, Nature, vol. 14(1), pages 1-14, December.
    9. Peter Zhukovsky & Earvin S. Tio & Gillian Coughlan & David A. Bennett & Yanling Wang & Timothy J. Hohman & Diego A. Pizzagalli & Benoit H. Mulsant & Aristotle N. Voineskos & Daniel Felsky, 2024. "Genetic influences on brain and cognitive health and their interactions with cardiovascular conditions and depression," Nature Communications, Nature, vol. 15(1), pages 1-11, December.
    10. Yuki Ishikawa & Nao Tanaka & Yoshihide Asano & Masanari Kodera & Yuichiro Shirai & Mitsuteru Akahoshi & Minoru Hasegawa & Takashi Matsushita & Kazuyoshi Saito & Sei-ichiro Motegi & Hajime Yoshifuji & , 2024. "GWAS for systemic sclerosis identifies six novel susceptibility loci including one in the Fcγ receptor region," Nature Communications, Nature, vol. 15(1), pages 1-16, December.
    11. Jie Huang & Jennifer E. Huffman & Yunfeng Huang & Ítalo Valle & Themistocles L. Assimes & Sridharan Raghavan & Benjamin F. Voight & Chang Liu & Albert-László Barabási & Rose D. L. Huang & Qin Hui & Xu, 2022. "Genomics and phenomics of body mass index reveals a complex disease network," Nature Communications, Nature, vol. 13(1), pages 1-10, December.
    12. Andras Boeszoermenyi & Léa Bernaleau & Xudong Chen & Felix Kartnig & Min Xie & Haobo Zhang & Sensen Zhang & Maeva Delacrétaz & Anna Koren & Ann-Katrin Hopp & Vojtech Dvorak & Stefan Kubicek & Daniel A, 2023. "A conformation-locking inhibitor of SLC15A4 with TASL proteostatic anti-inflammatory activity," Nature Communications, Nature, vol. 14(1), pages 1-12, December.
    13. Xiaofeng Zhu & Yihe Yang & Noah Lorincz-Comi & Gen Li & Amy R. Bentley & Paul S. de Vries & Michael Brown & Alanna C. Morrison & Charles N. Rotimi & W. James Gauderman & Dabeeru C. Rao & Hugues Aschar, 2024. "An approach to identify gene-environment interactions and reveal new biological insight in complex traits," Nature Communications, Nature, vol. 15(1), pages 1-13, December.
    14. Lynne Krohn & Karl Heilbron & Cornelis Blauwendraat & Regina H. Reynolds & Eric Yu & Konstantin Senkevich & Uladzislau Rudakou & Mehrdad A. Estiar & Emil K. Gustavsson & Kajsa Brolin & Jennifer A. Rus, 2022. "Genome-wide association study of REM sleep behavior disorder identifies polygenic risk and brain expression effects," Nature Communications, Nature, vol. 13(1), pages 1-16, December.
    15. 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.
    16. Jakub Kopal & Kuldeep Kumar & Kimia Shafighi & Karin Saltoun & Claudia Modenato & Clara A. Moreau & Guillaume Huguet & Martineau Jean-Louis & Charles-Olivier Martin & Zohra Saci & Nadine Younis & Elis, 2024. "Using rare genetic mutations to revisit structural brain asymmetry," Nature Communications, Nature, vol. 15(1), pages 1-19, December.
    17. Zhiqiang Sha & Dick Schijven & Amaia Carrion-Castillo & Marc Joliot & Bernard Mazoyer & Simon E. Fisher & Fabrice Crivello & Clyde Francks, 2021. "The genetic architecture of structural left–right asymmetry of the human brain," Nature Human Behaviour, Nature, vol. 5(9), pages 1226-1239, September.
    18. Catherine M. Francis & Matthias E. Futschik & Jian Huang & Wenjia Bai & Muralidharan Sargurupremraj & Alexander Teumer & Monique M. B. Breteler & Enrico Petretto & Amanda S. R. Ho & Philippe Amouyel &, 2022. "Genome-wide associations of aortic distensibility suggest causality for aortic aneurysms and brain white matter hyperintensities," Nature Communications, Nature, vol. 13(1), pages 1-18, December.
    19. Palwende Romuald Boua & Jean-Tristan Brandenburg & Ananyo Choudhury & Hermann Sorgho & Engelbert A. Nonterah & Godfred Agongo & Gershim Asiki & Lisa Micklesfield & Solomon Choma & Francesc Xavier Góme, 2022. "Genetic associations with carotid intima-media thickness link to atherosclerosis with sex-specific effects in sub-Saharan Africans," Nature Communications, Nature, vol. 13(1), pages 1-11, December.
    20. Antje Häder & Sascha Schäuble & Jan Gehlen & Nadja Thielemann & Benedikt C. Buerfent & Vitalia Schüller & Timo Hess & Thomas Wolf & Julia Schröder & Michael Weber & Kerstin Hünniger & Jürgen Löffler &, 2023. "Pathogen-specific innate immune response patterns are distinctly affected by genetic diversity," Nature Communications, Nature, vol. 14(1), pages 1-15, 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:14:y:2023:i:1:d:10.1038_s41467-023-36678-8. 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.