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

Lookup NU author(s): Dr Wei-Yu Lin, Dr Sarah Fordham, Dr Nicola Sunter, Dr Claire Elstob, Dr Yaobo Xu, Dr Catherine Park, Dr Thahira Rahman, Dr Gail Jones, Dr Helen Marr, Professor Graham Jackson, Dr Tobias Menne, Professor Matthew CollinORCiD, Professor Olaf Heidenreich, Abrar Alharbi, Jean Norden, Professor Anne Dickinson, Elizabeth Douglas, Dr Clare LendremORCiD, Professor Ann DalyORCiD, Professor Heather Cordell, Dr Rebecca Darlay, Professor James Allan

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Abstract

© 2021, The Author(s).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).

Publication metadata

Author(s): Lin W-Y, Fordham SE, Hungate E, Sunter NJ, Elstob C, Xu Y, Park C, Quante A, Strauch K, Gieger C, Skol A, Rahman T, Sucheston-Campbell L, Wang J, Hahn T, Clay-Gilmour AI, Jones GL, Marr HJ, Jackson GH, Menne T, Collin M, Ivey A, Hills RK, Burnett AK, Russell NH, Fitzgibbon J, Larson RA, Le Beau MM, Stock W, Heidenreich O, Alharbi A, Allsup DJ, Houlston RS, Norden J, Dickinson AM, Douglas E, Lendrem C, Daly AK, Palm L, Piechocki K, Jeffries S, Bornhauser M, Rollig C, Altmann H, Ruhnke L, Kunadt D, Wagenfuhr L, Cordell HJ, Darlay R, Andersen MK, Fontana MC, Martinelli G, Marconi G, Sanz MA, Cervera J, Gomez-Segui I, Cluzeau T, Moreilhon C, Raynaud S, Sill H, Voso MT, Lo-Coco F, Dombret H, Cheok M, Preudhomme C, Gale RE, Linch D, Gaal-Wesinger J, Masszi A, Nowak D, Hofmann W-K, Gilkes A, Porkka K, Milosevic Feenstra JD, Kralovics R, Grimwade D, Meggendorfer M, Haferlach T, Krizsan S, Bodor C, Stolzel F, Onel K, Allan JM

Publication type: Article

Publication status: Published

Journal: Nature Communications

Year: 2021

Volume: 12

Issue: 1

Print publication date: 01/12/2021

Online publication date: 29/10/2021

Acceptance date: 01/10/2021

Date deposited: 13/07/2023

ISSN (electronic): 2041-1723

Publisher: Nature Research

URL: https://doi.org/10.1038/s41467-021-26551-x

DOI: 10.1038/s41467-021-26551-x

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