IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v15y2024i1d10.1038_s41467-023-44512-4.html
   My bibliography  Save this article

Polygenic risk score for ulcerative colitis predicts immune checkpoint inhibitor-mediated colitis

Author

Listed:
  • Pooja Middha

    (University of California San Francisco)

  • Rohit Thummalapalli

    (Memorial Sloan Kettering Cancer Center)

  • Michael J. Betti

    (Vanderbilt University Medical Center)

  • Lydia Yao

    (Vanderbilt University Medical Center)

  • Zoe Quandt

    (University of California San Francisco
    University of California San Francisco)

  • Karmugi Balaratnam

    (Princess Margaret Cancer Centre)

  • Cosmin A. Bejan

    (Vanderbilt University Medical Center)

  • Eduardo Cardenas

    (University of California San Francisco)

  • Christina J. Falcon

    (Fiona and Stanley Druckenmiller Center for Lung Cancer Research, Memorial Sloan Kettering Cancer Center)

  • David M. Faleck

    (Memorial Sloan Kettering Cancer Center)

  • Matthew A. Gubens

    (University of California San Francisco
    University of California San Francisco)

  • Scott Huntsman

    (University of California San Francisco)

  • Douglas B. Johnson

    (Vanderbilt University Medical Center)

  • Linda Kachuri

    (Stanford University School of Medicine
    Stanford University of Medicine)

  • Khaleeq Khan

    (Princess Margaret Cancer Centre)

  • Min Li

    (University of California San Francisco)

  • Christine M. Lovly

    (Vanderbilt University Medical Center and Vanderbilt Ingram Cancer Center)

  • Megan H. Murray

    (Vanderbilt University Medical Center)

  • Devalben Patel

    (Princess Margaret Cancer Centre)

  • Kristin Werking

    (Vanderbilt University Medical Center)

  • Yaomin Xu

    (Vanderbilt University Medical Center)

  • Luna Jia Zhan

    (Princess Margaret Cancer Centre)

  • Justin M. Balko

    (Vanderbilt University Medical Center)

  • Geoffrey Liu

    (Princess Margaret Cancer Centre
    Temerty School of Medicine
    University of Toronto)

  • Melinda C. Aldrich

    (Vanderbilt University Medical Center)

  • Adam J. Schoenfeld

    (Thoracic Oncology Service, Memorial Sloan Kettering Cancer Center)

  • Elad Ziv

    (University of California San Francisco
    University of California San Francisco
    University of California San Francisco
    University of California San Francisco)

Abstract

Immune checkpoint inhibitor-mediated colitis (IMC) is a common adverse event of treatment with immune checkpoint inhibitors (ICI). We hypothesize that genetic susceptibility to Crohn’s disease (CD) and ulcerative colitis (UC) predisposes to IMC. In this study, we first develop a polygenic risk scores for CD (PRSCD) and UC (PRSUC) in cancer-free individuals and then test these PRSs on IMC in a cohort of 1316 patients with ICI-treated non-small cell lung cancer and perform a replication in 873 ICI-treated pan-cancer patients. In a meta-analysis, the PRSUC predicts all-grade IMC (ORmeta=1.35 per standard deviation [SD], 95% CI = 1.12–1.64, P = 2×10−03) and severe IMC (ORmeta=1.49 per SD, 95% CI = 1.18–1.88, P = 9×10−04). PRSCD is not associated with IMC. Furthermore, PRSUC predicts severe IMC among patients treated with combination ICIs (ORmeta=2.20 per SD, 95% CI = 1.07–4.53, P = 0.03). Overall, PRSUC can identify patients receiving ICI at risk of developing IMC and may be useful to monitor patients and improve patient outcomes.

Suggested Citation

  • Pooja Middha & Rohit Thummalapalli & Michael J. Betti & Lydia Yao & Zoe Quandt & Karmugi Balaratnam & Cosmin A. Bejan & Eduardo Cardenas & Christina J. Falcon & David M. Faleck & Matthew A. Gubens & S, 2024. "Polygenic risk score for ulcerative colitis predicts immune checkpoint inhibitor-mediated colitis," Nature Communications, Nature, vol. 15(1), pages 1-10, December.
    • Handle: RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-023-44512-4
    DOI: 10.1038/s41467-023-44512-4
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/s41467-023-44512-4
    File Function: Abstract
    Download Restriction: no
    File URL: https://libkey.io/10.1038/s41467-023-44512-4?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. Zia Khan & Christian Hammer & Jonathan Carroll & Flavia Nucci & Sergio Ley Acosta & Vidya Maiya & Tushar Bhangale & Julie Hunkapiller & Ira Mellman & Matthew L. Albert & Mark I. McCarthy & G. Scott Ch, 2021. "Genetic variation associated with thyroid autoimmunity shapes the systemic immune response to PD-1 checkpoint blockade," Nature Communications, Nature, vol. 12(1), pages 1-12, December.
    2. Michael Conroy & Jarushka Naidoo, 2022. "Immune-related adverse events and the balancing act of immunotherapy," Nature Communications, Nature, vol. 13(1), pages 1-4, December.
    3. Clare Bycroft & Colin Freeman & Desislava Petkova & Gavin Band & Lloyd T. Elliott & Kevin Sharp & Allan Motyer & Damjan Vukcevic & Olivier Delaneau & Jared O’Connell & Adrian Cortes & Samantha Welsh &, 2018. "The UK Biobank resource with deep phenotyping and genomic data," Nature, Nature, vol. 562(7726), pages 203-209, October.
    4. Seungho Cook & Wanson Choi & Hyunjoon Lim & Yang Luo & Kunhee Kim & Xiaoming Jia & Soumya Raychaudhuri & Buhm Han, 2021. "Accurate imputation of human leukocyte antigens with CookHLA," Nature Communications, Nature, vol. 12(1), pages 1-11, December.
    5. Caroline Robert, 2020. "A decade of immune-checkpoint inhibitors in cancer therapy," Nature Communications, Nature, vol. 11(1), pages 1-3, December.
    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. Gunther Glehr & Paloma Riquelme & Katharina Kronenberg & Robert Lohmayer & Víctor J. López-Madrona & Michael Kapinsky & Hans J. Schlitt & Edward K. Geissler & Rainer Spang & Sebastian Haferkamp & Jame, 2024. "Restricting datasets to classifiable samples augments discovery of immune disease biomarkers," Nature Communications, Nature, vol. 15(1), pages 1-21, December.
    2. Matteo Di Scipio & Mohammad Khan & Shihong Mao & Michael Chong & Conor Judge & Nazia Pathan & Nicolas Perrot & Walter Nelson & Ricky Lali & Shuang Di & Robert Morton & Jeremy Petch & Guillaume Paré, 2023. "A versatile, fast and unbiased method for estimation of gene-by-environment interaction effects on biobank-scale datasets," Nature Communications, Nature, vol. 14(1), pages 1-15, December.
    3. Jacob Joseph & Chang Liu & Qin Hui & Krishna Aragam & Zeyuan Wang & Brian Charest & Jennifer E. Huffman & Jacob M. Keaton & Todd L. Edwards & Serkalem Demissie & Luc Djousse & Juan P. Casas & J. Micha, 2022. "Genetic architecture of heart failure with preserved versus reduced ejection fraction," Nature Communications, Nature, vol. 13(1), pages 1-14, December.
    4. Vincent Michaud & Eulalie Lasseaux & David J. Green & Dave T. Gerrard & Claudio Plaisant & Tomas Fitzgerald & Ewan Birney & Benoît Arveiler & Graeme C. Black & Panagiotis I. Sergouniotis, 2022. "The contribution of common regulatory and protein-coding TYR variants to the genetic architecture of albinism," Nature Communications, Nature, vol. 13(1), pages 1-8, December.
    5. 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.
    6. Dick Schijven & Sourena Soheili-Nezhad & Simon E. Fisher & Clyde Francks, 2024. "Exome-wide analysis implicates rare protein-altering variants in human handedness," Nature Communications, Nature, vol. 15(1), pages 1-12, December.
    7. Lili Liu & Atlas Khan & Elena Sanchez-Rodriguez & Francesca Zanoni & Yifu Li & Nicholas Steers & Olivia Balderes & Junying Zhang & Priya Krithivasan & Robert A. LeDesma & Clara Fischman & Scott J. Heb, 2022. "Genetic regulation of serum IgA levels and susceptibility to common immune, infectious, kidney, and cardio-metabolic traits," Nature Communications, Nature, vol. 13(1), pages 1-17, December.
    8. Shahram Bahrami & Kaja Nordengen & Jaroslav Rokicki & Alexey A. Shadrin & Zillur Rahman & Olav B. Smeland & Piotr P. Jaholkowski & Nadine Parker & Pravesh Parekh & Kevin S. O’Connell & Torbjørn Elvsås, 2024. "The genetic landscape of basal ganglia and implications for common brain disorders," Nature Communications, Nature, vol. 15(1), pages 1-14, December.
    9. Marta Alcalde-Herraiz & JunQing Xie & Danielle Newby & Clara Prats & Dipender Gill & María Gordillo-Marañón & Daniel Prieto-Alhambra & Martí Català & Albert Prats-Uribe, 2024. "Effect of genetically predicted sclerostin on cardiovascular biomarkers, risk factors, and disease outcomes," Nature Communications, Nature, vol. 15(1), pages 1-12, December.
    10. Sylvia Hartmann & Summaira Yasmeen & Benjamin M. Jacobs & Spiros Denaxas & Munir Pirmohamed & Eric R. Gamazon & Mark J. Caulfield & Harry Hemingway & Maik Pietzner & Claudia Langenberg, 2023. "ADRA2A and IRX1 are putative risk genes for Raynaud’s phenomenon," Nature Communications, Nature, vol. 14(1), pages 1-11, December.
    11. Elizabeth C. Goode & Laura Fachal & Nikolaos Panousis & Loukas Moutsianas & Rebecca E. McIntyre & Benjamin Yu Hang Bai & Norihito Kawasaki & Alexandra Wittmann & Tim Raine & Simon M. Rushbrook & Carl , 2024. "Fine-mapping and molecular characterisation of primary sclerosing cholangitis genetic risk loci," Nature Communications, Nature, vol. 15(1), pages 1-14, December.
    12. Mit Shah & Marco H. A. Inácio & Chang Lu & Pierre-Raphaël Schiratti & Sean L. Zheng & Adam Clement & Antonio Marvao & Wenjia Bai & Andrew P. King & James S. Ware & Martin R. Wilkins & Johanna Mielke &, 2023. "Environmental and genetic predictors of human cardiovascular ageing," Nature Communications, Nature, vol. 14(1), pages 1-15, December.
    13. Mathias Seviiri & Matthew H. Law & Jue-Sheng Ong & Puya Gharahkhani & Pierre Fontanillas & Catherine M. Olsen & David C. Whiteman & Stuart MacGregor, 2022. "A multi-phenotype analysis reveals 19 susceptibility loci for basal cell carcinoma and 15 for squamous cell carcinoma," Nature Communications, Nature, vol. 13(1), pages 1-14, December.
    14. Zhaotong Lin & Wei Pan, 2024. "A robust cis-Mendelian randomization method with application to drug target discovery," Nature Communications, Nature, vol. 15(1), pages 1-14, December.
    15. Qianqian Ming & Daniel Antfolk & David A. Price & Anna Manturova & Elliot Medina & Srishti Singh & Charlotte Mason & Timothy H. Tran & Keiran S. M. Smalley & Daisy W. Leung & Vincent C. Luca, 2024. "Structural basis for mouse LAG3 interactions with the MHC class II molecule I-Ab," Nature Communications, Nature, vol. 15(1), pages 1-11, December.
    16. Zhening Liu & Hangkai Huang & Jiarong Xie & Yingying Xu & Chengfu Xu, 2024. "Circulating fatty acids and risk of hepatocellular carcinoma and chronic liver disease mortality in the UK Biobank," Nature Communications, Nature, vol. 15(1), pages 1-10, December.
    17. Junqing Xie & Shuo Feng & Xintong Li & Ester Gea-Mallorquí & Albert Prats-Uribe & Dani Prieto-Alhambra, 2022. "Comparative effectiveness of the BNT162b2 and ChAdOx1 vaccines against Covid-19 in people over 50," Nature Communications, Nature, vol. 13(1), pages 1-8, December.
    18. Rongtao Jiang & Stephanie Noble & Matthew Rosenblatt & Wei Dai & Jean Ye & Shu Liu & Shile Qi & Vince D. Calhoun & Jing Sui & Dustin Scheinost, 2024. "The brain structure, inflammatory, and genetic mechanisms mediate the association between physical frailty and depression," Nature Communications, Nature, vol. 15(1), pages 1-11, December.
    19. Erik Schoenmakers & Federica Marelli & Helle F. Jørgensen & W. Edward Visser & Carla Moran & Stefan Groeneweg & Carolina Avalos & Sean J. Jurgens & Nichola Figg & Alison Finigan & Neha Wali & Maura Ag, 2023. "Selenoprotein deficiency disorder predisposes to aortic aneurysm formation," Nature Communications, Nature, vol. 14(1), pages 1-14, December.
    20. Harry D Green & Alistair Jones & Jonathan P Evans & Andrew R Wood & Robin N Beaumont & Jessica Tyrrell & Timothy M Frayling & Christopher Smith & Michael N Weedon, 2021. "A genome-wide association study identifies 5 loci associated with frozen shoulder and implicates diabetes as a causal risk factor," PLOS Genetics, Public Library of Science, vol. 17(6), pages 1-13, June.

    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_s41467-023-44512-4. 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.