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Genome-wide association study identifies susceptibility loci for acute myeloid leukemia

Author

Listed:
  • Wei-Yu Lin

    (Newcastle University)

  • Sarah E. Fordham

    (Newcastle University)

  • Eric Hungate

    (University of Chicago)

  • Nicola J. Sunter

    (Newcastle University)

  • Claire Elstob

    (Newcastle University)

  • Yaobo Xu

    (Newcastle University)

  • Catherine Park

    (Newcastle University)

  • Anne Quante

    (Helmholtz Zentrum München, German Research Center for Environmental Health
    Ludwig-Maximilians-Universität München, Chair of Genetic Epidemiology, IBE, Faculty of Medicine)

  • Konstantin Strauch

    (Helmholtz Zentrum München, German Research Center for Environmental Health
    Ludwig-Maximilians-Universität München, Chair of Genetic Epidemiology, IBE, Faculty of Medicine)

  • Christian Gieger

    (Ludwig-Maximilians-Universität München, Chair of Genetic Epidemiology, IBE, Faculty of Medicine)

  • Andrew Skol

    (University of Chicago)

  • Thahira Rahman

    (Newcastle University)

  • Lara Sucheston-Campbell

    (College of Pharmacy, The Ohio State University)

  • Junke Wang

    (College of Pharmacy, The Ohio State University)

  • Theresa Hahn

    (Roswell Park Cancer Institute)

  • Alyssa I. Clay-Gilmour

    (University of South Carolina)

  • Gail L. Jones

    (Department of Haematology, Freeman Hospital, Newcastle upon Tyne Hospitals National Health Service Foundation Trust)

  • Helen J. Marr

    (Department of Haematology, Freeman Hospital, Newcastle upon Tyne Hospitals National Health Service Foundation Trust)

  • Graham H. Jackson

    (Department of Haematology, Freeman Hospital, Newcastle upon Tyne Hospitals National Health Service Foundation Trust)

  • Tobias Menne

    (Department of Haematology, Freeman Hospital, Newcastle upon Tyne Hospitals National Health Service Foundation Trust)

  • Mathew Collin

    (Department of Haematology, Freeman Hospital, Newcastle upon Tyne Hospitals National Health Service Foundation Trust)

  • Adam Ivey

    (Department of Medical and Molecular Genetics, King’s College Medical School)

  • Robert K. Hills

    (University of Oxford)

  • Alan K. Burnett

    (Paul O’Gorman Leukaemia Research Centre, University of Glasgow)

  • Nigel H. Russell

    (Department of Haematology, Nottingham University Hospitals NHS Trust)

  • Jude Fitzgibbon

    (Barts Cancer Institute, Queen Mary University of London)

  • Richard A. Larson

    (University of Chicago)

  • Michelle M. Le Beau

    (University of Chicago)

  • Wendy Stock

    (University of Chicago)

  • Olaf Heidenreich

    (Newcastle University)

  • Abrar Alharbi

    (Newcastle University)

  • David J. Allsup

    (Centre for Atherothrombosis and Metabolic Disease, Hull York Medical School)

  • Richard S. Houlston

    (Division of Genetics and Epidemiology, The Institute of Cancer Research)

  • Jean Norden

    (Newcastle University)

  • Anne M. Dickinson

    (Newcastle University)

  • Elisabeth Douglas

    (Newcastle University)

  • Clare Lendrem

    (Newcastle University)

  • Ann K. Daly

    (Newcastle University)

  • Louise Palm

    (West Midlands Regional Genetics Laboratory, Birmingham Women’s Hospital)

  • Kim Piechocki

    (West Midlands Regional Genetics Laboratory, Birmingham Women’s Hospital)

  • Sally Jeffries

    (West Midlands Regional Genetics Laboratory, Birmingham Women’s Hospital)

  • Martin Bornhäuser

    (The Rayne Institute, King’s College London
    National Center for Tumor Diseases NCT, Partner site Dresden
    Medizinische Klinik und Poliklinik I, University Hospital Carl Gustav Carus Dresden, Technical University of Dresden)

  • Christoph Röllig

    (Medizinische Klinik und Poliklinik I, University Hospital Carl Gustav Carus Dresden, Technical University of Dresden)

  • Heidi Altmann

    (Medizinische Klinik und Poliklinik I, University Hospital Carl Gustav Carus Dresden, Technical University of Dresden)

  • Leo Ruhnke

    (Medizinische Klinik und Poliklinik I, University Hospital Carl Gustav Carus Dresden, Technical University of Dresden)

  • Desiree Kunadt

    (Medizinische Klinik und Poliklinik I, University Hospital Carl Gustav Carus Dresden, Technical University of Dresden)

  • Lisa Wagenführ

    (Medizinische Klinik und Poliklinik I, University Hospital Carl Gustav Carus Dresden, Technical University of Dresden)

  • Heather J. Cordell

    (Newcastle University)

  • Rebecca Darlay

    (Newcastle University)

  • Mette K. Andersen

    (University Hospital Rigshospitalet)

  • Maria C. Fontana

    (University of Bologna
    IRCCS Istituto Romagnolo per lo Studio dei Tumori (IRST) “Dino Amadori”)

  • Giovanni Martinelli

    (IRCCS Istituto Romagnolo per lo Studio dei Tumori (IRST) “Dino Amadori”)

  • Giovanni Marconi

    (IRCCS Istituto Romagnolo per lo Studio dei Tumori (IRST) “Dino Amadori”)

  • Miguel A. Sanz

    (Hematology Service, Hospital Universitario y Politécnico La Fe
    CIBERONC, Instituto de Salud Carlos III)

  • José Cervera

    (Hematology Service, Hospital Universitario y Politécnico La Fe
    CIBERONC, Instituto de Salud Carlos III)

  • Inés Gómez-Seguí

    (Hematology Service, Hospital Universitario y Politécnico La Fe
    CIBERONC, Instituto de Salud Carlos III)

  • Thomas Cluzeau

    (Cote d’Azur University, CHU of Nice)

  • Chimène Moreilhon

    (Cote d’Azur University, CHU of Nice)

  • Sophie Raynaud

    (Cote d’Azur University, CHU of Nice)

  • Heinz Sill

    (Medical University of Graz)

  • Maria Teresa Voso

    (Università di Roma Tor Vergata, Dipartimento di Biomedicina e Prevenzione)

  • Francesco Lo-Coco

    (Università di Roma Tor Vergata, Dipartimento di Biomedicina e Prevenzione)

  • Hervé Dombret

    (Hôpital Saint-Louis, Institut Universitaire d’Hématologie, Université Paris Diderot)

  • Meyling Cheok

    (Univ. Lille, Inserm, CHU Lille, UMR-S 1172 - JPArc - Centre de Recherche Jean-Pierre AUBERT Neurosciences et Cancer)

  • Claude Preudhomme

    (Univ. Lille, Inserm, CHU Lille, UMR-S 1172 - JPArc - Centre de Recherche Jean-Pierre AUBERT Neurosciences et Cancer)

  • Rosemary E. Gale

    (University College London Cancer Institute)

  • David Linch

    (University College London Cancer Institute)

  • Julia Gaal-Wesinger

    (Semmewleis University)

  • Andras Masszi

    (Semmewleis University)

  • Daniel Nowak

    (Heidelberg University)

  • Wolf-Karsten Hofmann

    (Heidelberg University)

  • Amanda Gilkes

    (University of Cardiff)

  • Kimmo Porkka

    (Hematology Research Unit Helsinki, University of Helsinki)

  • Jelena D. Milosevic Feenstra

    (Medical University of Vienna)

  • Robert Kralovics

    (Medical University of Vienna)

  • David Grimwade

    (Department of Medical and Molecular Genetics, King’s College Medical School)

  • Manja Meggendorfer

    (MLL Munich Leukemia Laboratory)

  • Torsten Haferlach

    (MLL Munich Leukemia Laboratory)

  • Szilvia Krizsán

    (Semmelweis University)

  • Csaba Bödör

    (Semmelweis University)

  • Friedrich Stölzel

    (Medizinische Klinik und Poliklinik I, University Hospital Carl Gustav Carus Dresden, Technical University of Dresden)

  • Kenan Onel

    (Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai)

  • James M. Allan

    (Newcastle University)

Abstract

Acute myeloid leukemia (AML) is a hematological malignancy with an undefined heritable risk. Here we perform a meta-analysis of three genome-wide association studies, with replication in a fourth study, incorporating a total of 4018 AML cases and 10488 controls. We identify a genome-wide significant risk locus for AML at 11q13.2 (rs4930561; P = 2.15 × 10−8; KMT5B). We also identify a genome-wide significant risk locus for the cytogenetically normal AML sub-group (N = 1287) at 6p21.32 (rs3916765; P = 1.51 × 10−10; HLA). Our results inform on AML etiology and identify putative functional genes operating in histone methylation (KMT5B) and immune function (HLA).

Suggested Citation

  • Wei-Yu Lin & Sarah E. Fordham & Eric Hungate & Nicola J. Sunter & Claire Elstob & Yaobo Xu & Catherine Park & Anne Quante & Konstantin Strauch & Christian Gieger & Andrew Skol & Thahira Rahman & Lara , 2021. "Genome-wide association study identifies susceptibility loci for acute myeloid leukemia," Nature Communications, Nature, vol. 12(1), pages 1-10, December.
    • Handle: RePEc:nat:natcom:v:12:y:2021:i:1:d:10.1038_s41467-021-26551-x
    DOI: 10.1038/s41467-021-26551-x
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    References listed on IDEAS

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    1. Syed A. Mian & Kevin Rouault-Pierre & Alexander E. Smith & Thomas Seidl & Irene Pizzitola & Aytug Kizilors & Austin G. Kulasekararaj & Dominique Bonnet & Ghulam J. Mufti, 2015. "SF3B1 mutant MDS-initiating cells may arise from the haematopoietic stem cell compartment," Nature Communications, Nature, vol. 6(1), pages 1-14, December.
    2. Amit Sud & Hauke Thomsen & Philip J. Law & Asta Försti & Miguel Inacio da Silva Filho & Amy Holroyd & Peter Broderick & Giulia Orlando & Oleg Lenive & Lauren Wright & Rosie Cooke & Douglas Easton & Pa, 2017. "Genome-wide association study of classical Hodgkin lymphoma identifies key regulators of disease susceptibility," Nature Communications, Nature, vol. 8(1), pages 1-11, December.
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    Cited by:

    1. Simona Pagliuca & Carmelo Gurnari & Colin Hercus & Sébastien Hergalant & Sanghee Hong & Adele Dhuyser & Maud D’Aveni & Alice Aarnink & Marie Thérèse Rubio & Pierre Feugier & Francesca Ferraro & Hetty , 2023. "Leukemia relapse via genetic immune escape after allogeneic hematopoietic cell transplantation," Nature Communications, Nature, vol. 14(1), pages 1-12, December.

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