Genome-wide association study identifies susceptibility loci for acute myeloid leukemia
Wei‐Yu Lin, Sarah Fordham, Eric A. Hungate, Nicola J. Sunter, Claire 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 Jones, Helen Marr, Graham 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 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, Desireé Kunadt, Lisa Wagenführ, Heather J. Cordell, Rebecca Darlay, Mette Klarskov Andersen, Maria Chiara Fontana, Giovanni Martinelli, Giovanni Marconi, Miguel Á. 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 C. Linch, Julia Gaal-Wesinger, András Masszi, Daniel Nowak, Wolf‐Karsten Hofmann, Amanda Gilkes, Kimmo Porkka, Jelena D. Milosevic Feenstra, Róbert Královics, David Grimwade, Manja Meggendorfer, Torsten Haferlach, Szilvia Krizsán, Csaba Bödör, Friedrich Stölzel, Kenan Onel, James M. Allan
Abstract
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 ).