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

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.; Collin, M.; Ivey, A.; Hills, R. K.; Burnett, A. K.; Russell, N. H.; Fitzgibbon, J.; Larson, R. A.; Le Beau, M. M.; Stock, W.; Heidenreich, O.; Alharbi, A.; Allsup, D. J.; Houlston, R. S.; Norden, J.; Dickinson, A. M.; Douglas, E.; Lendrem, C.; Daly, A. K.; Palm, L.; Piechocki, K.; Jeffries, S.; Bornhauser, M.; Rollig, C.; Altmann, H.; Ruhnke, L.; Kunadt, D.; Wagenfuhr, L.; Cordell, H. J.; Darlay, R.; Andersen, M. K.; Fontana, M. C.; Martinelli, G.; Marconi, G.; Sanz, M. A.; Cervera, J.; Gomez-Segui, I.; Cluzeau, T.; Moreilhon, C.; Raynaud, S.; Sill, H.; Voso, M. T.; Lo-Coco, F.; Dombret, H.; Cheok, M.; Preudhomme, C.; Gale, R. E.; Linch, D.; Gaal-Wesinger, J.; Masszi, A.; Nowak, D.; Hofmann, W. -K.; Gilkes, A.; Porkka, K.; Milosevic Feenstra, J. D.; Kralovics, R.; Grimwade, D.; Meggendorfer, M.; Haferlach, T.; Krizsan, S.; Bodor, C.; Stolzel, F.; Onel, K.; Allan, J. M.

doi:10.1038/s41467-021-26551-x

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).

Lin W.-Y., Fordham S.E., Hungate E., Sunter N.J., Elstob C., Xu Y., et al. (2021). Genome-wide association study identifies susceptibility loci for acute myeloid leukemia. NATURE COMMUNICATIONS, 12(1), 0-0 [10.1038/s41467-021-26551-x].