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Inherited myeloproliferative neoplasm risk affects haematopoietic stem cells

Author

Listed:
  • Erik L. Bao

    (Harvard Medical School
    Harvard Medical School
    Broad Institute of MIT and Harvard
    Harvard Medical School)

  • Satish K. Nandakumar

    (Harvard Medical School
    Harvard Medical School
    Broad Institute of MIT and Harvard)

  • Xiaotian Liao

    (Harvard Medical School
    Harvard Medical School
    Broad Institute of MIT and Harvard)

  • Alexander G. Bick

    (Broad Institute of MIT and Harvard
    Massachusetts General Hospital
    Massachusetts General Hospital
    VA Boston Healthcare, Section of Cardiology)

  • Juha Karjalainen

    (University of Helsinki)

  • Marcin Tabaka

    (Broad Institute of MIT and Harvard)

  • Olga I. Gan

    (University Health Network
    University of Toronto)

  • Aki S. Havulinna

    (University of Helsinki)

  • Tuomo T. J. Kiiskinen

    (University of Helsinki)

  • Caleb A. Lareau

    (Harvard Medical School
    Harvard Medical School
    Broad Institute of MIT and Harvard
    Harvard Medical School)

  • Aitzkoa L. Lapuente Portilla

    (Lund University)

  • Bo Li

    (Broad Institute of MIT and Harvard
    Massachusetts General Hospital)

  • Connor Emdin

    (Broad Institute of MIT and Harvard
    Massachusetts General Hospital)

  • Veryan Codd

    (Glenfield Hospital
    Glenfield Hospital)

  • Christopher P. Nelson

    (Glenfield Hospital
    Glenfield Hospital)

  • Christopher J. Walker

    (The Ohio State University Comprehensive Cancer Center)

  • Claire Churchhouse

    (Broad Institute of MIT and Harvard)

  • Albert Chapelle

    (The Ohio State University Comprehensive Cancer Center)

  • Daryl E. Klein

    (Yale University School of Medicine)

  • Björn Nilsson

    (Broad Institute of MIT and Harvard
    Lund University)

  • Peter W. F. Wilson

    (Atlanta VA Medical Center
    Emory Clinical Cardiovascular Research Institute)

  • Kelly Cho

    (Massachusetts Veterans Epidemiology Research and Information Center (MAVERIC), VA Boston Healthcare System
    Brigham and Women’s Hospital)

  • Saiju Pyarajan

    (Massachusetts Veterans Epidemiology Research and Information Center (MAVERIC), VA Boston Healthcare System)

  • J. Michael Gaziano

    (Massachusetts Veterans Epidemiology Research and Information Center (MAVERIC), VA Boston Healthcare System
    Brigham and Women’s Hospital)

  • Nilesh J. Samani

    (Glenfield Hospital
    Glenfield Hospital)

  • Aviv Regev

    (Broad Institute of MIT and Harvard
    Howard Hughes Medical Institute
    Massachusetts Institute of Technology)

  • Aarno Palotie

    (Broad Institute of MIT and Harvard
    University of Helsinki)

  • Benjamin M. Neale

    (Broad Institute of MIT and Harvard)

  • John E. Dick

    (University Health Network
    University of Toronto)

  • Pradeep Natarajan

    (Broad Institute of MIT and Harvard
    Massachusetts General Hospital
    Massachusetts General Hospital)

  • Christopher J. O’Donnell

    (VA Boston Healthcare, Section of Cardiology
    Brigham and Women’s Hospital)

  • Mark J. Daly

    (Broad Institute of MIT and Harvard
    University of Helsinki)

  • Michael Milyavsky

    (Tel Aviv University)

  • Sekar Kathiresan

    (Broad Institute of MIT and Harvard
    Massachusetts General Hospital
    Verve Therapeutics)

  • Vijay G. Sankaran

    (Harvard Medical School
    Harvard Medical School
    Broad Institute of MIT and Harvard
    Harvard Stem Cell Institute)

Abstract

Myeloproliferative neoplasms (MPNs) are blood cancers that are characterized by the excessive production of mature myeloid cells and arise from the acquisition of somatic driver mutations in haematopoietic stem cells (HSCs). Epidemiological studies indicate a substantial heritable component of MPNs that is among the highest known for cancers1. However, only a limited number of genetic risk loci have been identified, and the underlying biological mechanisms that lead to the acquisition of MPNs remain unclear. Here, by conducting a large-scale genome-wide association study (3,797 cases and 1,152,977 controls), we identify 17 MPN risk loci (P

Suggested Citation

  • Erik L. Bao & Satish K. Nandakumar & Xiaotian Liao & Alexander G. Bick & Juha Karjalainen & Marcin Tabaka & Olga I. Gan & Aki S. Havulinna & Tuomo T. J. Kiiskinen & Caleb A. Lareau & Aitzkoa L. Lapuen, 2020. "Inherited myeloproliferative neoplasm risk affects haematopoietic stem cells," Nature, Nature, vol. 586(7831), pages 769-775, October.
    • Handle: RePEc:nat:nature:v:586:y:2020:i:7831:d:10.1038_s41586-020-2786-7
    DOI: 10.1038/s41586-020-2786-7
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    Citations

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    Cited by:

    1. Yun Liu & Shuangyan Liu & Jiarui Xin & Peiyi Qian & Shuli Guo & Xiaojun Xu & Dahui Wang & Lei Yang, 2022. "Telomere Length and Hearing Loss: A Two-Sample Mendelian Randomization," IJERPH, MDPI, vol. 19(15), pages 1-11, July.
    2. Derek W. Brown & Liam D. Cato & Yajie Zhao & Satish K. Nandakumar & Erik L. Bao & Eugene J. Gardner & Aubrey K. Hubbard & Alexander DePaulis & Thomas Rehling & Lei Song & Kai Yu & Stephen J. Chanock &, 2023. "Shared and distinct genetic etiologies for different types of clonal hematopoiesis," Nature Communications, Nature, vol. 14(1), pages 1-13, December.
    3. Giulia Schiroli & Vinay Kartha & Fabiana M. Duarte & Trine A. Kristiansen & Christina Mayerhofer & Rojesh Shrestha & Andrew Earl & Yan Hu & Tristan Tay & Catherine Rhee & Jason D. Buenrostro & David T, 2024. "Cell of origin epigenetic priming determines susceptibility to Tet2 mutation," Nature Communications, Nature, vol. 15(1), pages 1-20, December.
    4. Derek W. Brown & Weiyin Zhou & Youjin Wang & Kristine Jones & Wen Luo & Casey Dagnall & Kedest Teshome & Alyssa Klein & Tongwu Zhang & Shu-Hong Lin & Olivia W. Lee & Sairah Khan & Jacqueline B. Vo & A, 2022. "Germline-somatic JAK2 interactions are associated with clonal expansion in myelofibrosis," Nature Communications, Nature, vol. 13(1), pages 1-11, December.
    5. Jonathan D. Mosley & John P. Shelley & Alyson L. Dickson & Jacy Zanussi & Laura L. Daniel & Neil S. Zheng & Lisa Bastarache & Wei-Qi Wei & Mingjian Shi & Gail P. Jarvik & Elisabeth A. Rosenthal & Atla, 2024. "Clinical associations with a polygenic predisposition to benign lower white blood cell counts," Nature Communications, Nature, vol. 15(1), pages 1-12, December.

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