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

Wei‐Yu Lin; Sarah Elizabeth Fordham; Eric A. Hungate; Nicola J. Sunter; Claire J. Elstob; Yaobo Xu; Catherine Park; Anne S. Quante; Konstantin Strauch; Christian Gieger; Andrew D. Skol; Thahira Rahman; Lara E. Sucheston‐Campbell; Junke Wang; Theresa Hahn; Alyssa Clay‐Gilmour; Gail L. Jones; Helen J. Marr; Graham Hunter Jackson; Tobias Menne; Mathew Collin; Adam Ivey; Robert Kerrin Hills; Alan K. Burnett; Nigel H. Russell; Jude Fitzgibbon; Richard A. Larson; Michelle M. Le Beau; Wendy Stock; Olaf T Heidenreich

doi:10.1038/s41467-021-26551-x

Genetic & Genomic MedicineNature CommunicationsOct 29, 2021

Peer-reviewed journal article

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

Wei‐Yu Lin iD, Sarah Elizabeth Fordham iD, Eric A. Hungate, Nicola J. Sunter, Claire J. Elstob iD, Yaobo Xu iD, Catherine Park, Anne S. Quante iD, Konstantin Strauch iD, Christian Gieger iD, Andrew D. Skol iD, Thahira Rahman, Lara E. Sucheston‐Campbell iD, Junke Wang iD, Theresa Hahn iD, Alyssa Clay‐Gilmour iD, Gail L. Jones, Helen J. Marr, Graham Hunter Jackson iD, Tobias Menne iD, Mathew Collin iD, Adam Ivey, Robert Kerrin Hills iD, Alan K. Burnett iD, Nigel H. Russell iD, , James M. Allan iD

Abstract

Acute myeloid leukemia (AML) is a hematological malignancy with an undefined heritable risk. Here we performed 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 identified a genome-wide significant risk locus for AML at 11q13.2 (rs4930561; P = 2.15 x 10-8; KMT5B). We also identified a genome-wide significant risk locus for the cytogenetically normal AML sub-group (N=1287) at 6p21.32 (rs3916765; P = 1.51 x 10-10; HLA). Our results inform on AML etiology by identifying putative functional genes operating in histone methylation (KMT5B) and immune function (HLA).

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