Year: 2021
Type: review
Study design: Observational Study
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 ).
Source: Nature Communications
Authors: 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 Sucheston-Campbell, Junke Wang, Theresa Hahn, Alyssa I. Clay-Gilmour, Gail L. Jones, Helen J. Marr, Graham H. Jackson, Tobias Menne, Mathew Collin, Adam Ivey, Robert K. Hills, Alan K. Burnett, Nigel H. Russell, Jude Fitzgibbon, Richard A. Larson, Michelle M. Le Beau, Wendy Stock, Olaf Heidenreich, Abrar Alharbi, David J. Allsup, Richard S. Houlston, Jean Norden, Anne M. Dickinson, Elisabeth Douglas, Clare Lendrem, Ann K. Daly, Louise Palm, Kim Piechocki, Sally Jeffries, Martin Bornhäuser, Christoph Röllig, Heidi Altmann, Leo Ruhnke, Desiree Kunadt, Lisa Wagenführ, Heather J. Cordell, Rebecca Darlay, Mette K. Andersen, Maria C. Fontana, Giovanni Martinelli, Giovanni Marconi, Miguel A. Sanz, José Cervera, Inés Gómez-Seguí, Thomas Cluzeau, Chimène Moreilhon, Sophie Raynaud, Heinz Sill, Maria Teresa Voso, Francesco Lo-Coco, Hervé Dombret, Meyling Cheok, Claude Preudhomme, Rosemary E. Gale, David Linch, Julia Gaal-Wesinger, Andras Masszi, Daniel Nowak, Wolf-Karsten Hofmann, Amanda Gilkes, Kimmo Porkka, Jelena D. Milosevic Feenstra, Robert Kralovics, David Grimwade, Manja Meggendorfer, Torsten Haferlach, Szilvia Krizsán, Csaba Bödör, Friedrich Stölzel, Kenan Onel, James M. Allan
Institutions: Newcastle University, University of Chicago, Helmholtz Munich, Ludwig-Maximilians-Universität München, The Ohio State University, Roswell Park Comprehensive Cancer Center, University of South Carolina, National Health Service, Newcastle upon Tyne Hospitals NHS Foundation Trust, Freeman Hospital, King's College London, University of Oxford, University of Glasgow, Nottingham University Hospitals NHS Trust, Queen Mary University of London, Barts Cancer Institute, Hull York Medical School, Institute of Cancer Research, Birmingham Women's Hospital, University Hospital Carl Gustav Carus, Nationales Centrum für Tumorerkrankungen Dresden, Technische Universität Dresden, Rigshospitalet, Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori, University of Bologna, Instituto de Salud Carlos III, Hospital Universitari i Politècnic La Fe, Centro de Investigación Biomédica en Red de Cáncer, Centre Hospitalier Universitaire de Nice, Medical University of Graz, University of Rome Tor Vergata, Hôpital Saint-Louis, Université Paris Diderot, Institut Universitaire d'Hématologie, Inserm, Université de Lille, Centre Hospitalier Universitaire de Lille, Centre de Recherche Jean Pierre Aubert, University College London, Semmelweis University, Heidelberg University, Medizinische Fakultät Mannheim, Cardiff University, University of Helsinki, Helsinki University Hospital, Medical University of Vienna, Munich Leukemia Laboratory (Germany), Icahn School of Medicine at Mount Sinai
Language: English
Subfield: Hematology
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $5,560
Funders: Cancer Research UK, Newcastle University, Bundesministerium für Bildung und Forschung, Magyar Tudományos Akadémia, Associazione Italiana per la Ricerca sul Cancro, José Carreras Leukämie-Stiftung, Nemzeti Kutatási Fejlesztési és Innovációs Hivatal, Blood Cancer UK, Medical Research Council, Helmholtz Zentrum München, National Research, Development and Innovation Office, National Heart, Lung, and Blood Institute, National Cancer Institute
Awards: Genetic susceptibility to unrelated donor stem cell transplant-related mortality, G2308955452, G290804699, G4002205913, G5067035887, G522970363, G5430722778, G5576324611, G6030162275, G6313988072, Genetic susceptibility to acute lymphocytic and myeloid leukemia, G7021488791, G7748129607, G8435462991, G8696801283, G8760335370, G8816475545
OpenAlex ID: W3209062845