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...

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., Park, C., Quante, A., Strauch, K., Gieger, C., Skol, A., Rahman, T., Sucheston-Campbell, L., Wang, J., Hahn, T., Clay-Gilmour, A. I., Jones, G. L., Marr, H. J., Jackson, G. H., Menne, T., …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: Nov 1, 2021
• 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