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

Lin, Wei Yu; Fordham, Sarah E.; Hungate, Eric; Sunter, Nicola J.; Elstob, Claire; Xu, Yaobo; Park, Catherine; Quante, Anne; Strauch, Konstantin; Gieger, Christian; Skol, Andrew; Rahman, Thahira; Sucheston-Campbell, Lara; Wang, Junke; Hahn, Theresa; Clay-Gilmour, Alyssa I.; Jones, Gail L.; Marr, Helen J.; Jackson, Graham H.; Menne, Tobias; Collin, Mathew; Ivey, Adam; Hills, Robert K.; Burnett, Alan K.; Russell, Nigel H.; Fitzgibbon, Jude; Larson, Richard A.; Le Beau, Michelle M.; Stock, Wendy; Heidenreich, Olaf; Alharbi, Abrar; Allsup, David J.; Houlston, Richard S.; Norden, Jean; Dickinson, Anne M.; Douglas, Elisabeth; Lendrem, Clare; Daly, Ann K.; Palm, Louise; Piechocki, Kim; Jeffries, Sally; Bornhäuser, Martin; Röllig, Christoph; Altmann, Heidi; Ruhnke, Leo; Kunadt, Desiree; Wagenführ, Lisa; Cordell, Heather J.; Darlay, Rebecca; Andersen, Mette K.; Fontana, Maria C.; Martinelli, Giovanni; Marconi, Giovani; Sanz, Miguel A.; Cervera, José; Gómez-Seguí, Inés; Cluzeau, Thomas; Moreilhon...

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

Profile Image

Dr David Allsup D.J.Allsup@hull.ac.uk
Senior Lecturer in Haematology and Honorary Consultant

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

Giovani 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



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).

Citation

Lin, W. Y., Fordham, S. E., Hungate, E., Sunter, N. J., Elstob, C., Xu, Y., …Allan, J. M. (2021). Genome-wide association study identifies susceptibility loci for acute myeloid leukemia. Nature communications, 12(1), Article 6233. https://doi.org/10.1038/s41467-021-26551-x

Journal Article Type Article
Acceptance Date Oct 1, 2021
Online Publication Date Oct 29, 2021
Publication Date 2021-12
Deposit Date Nov 1, 2021
Publicly Available Date Mar 29, 2024
Journal Nature Communications
Electronic ISSN 2041-1723
Publisher Nature Publishing Group
Peer Reviewed Peer Reviewed
Volume 12
Issue 1
Article Number 6233
DOI https://doi.org/10.1038/s41467-021-26551-x
Keywords Acute myeloid leukaemia; Cancer genomics; Risk factors
Public URL https://hull-repository.worktribe.com/output/3865990

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© The Author(s) 2021.
Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/ licenses/by/4.0/.




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