Genome-wide association study identifies susceptibility loci for acute myeloid leukemia.
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., Bornhäuser M., Röllig C., Altmann H., Ruhnke L., Kunadt D., Wagenführ L., Cordell HJ., Darlay R., Andersen MK., Fontana MC., Martinelli G., Marconi G., Sanz MA., Cervera J., Gómez-Seguí 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., Krizsán S., Bödör C., Stölzel F., Onel K., Allan JM.
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).