Genome-wide association study identifies susceptibility loci for acute myeloid leukemia.
Wei-Yu LinSarah E FordhamEric HungateNicola J SunterClaire ElstobYaobo XuCatherine ParkAnne QuanteKonstantin StrauchChristian GiegerAndrew SkolThahira RahmanLara Sucheston-CampbellJunke WangTheresa HahnAlyssa I Clay-GilmourGail L JonesHelen J MarrGraham H JacksonTobias MenneMatthew CollinAdam IveyRobert K HillsAlan K BurnettNigel H RussellJude FitzgibbonRichard A LarsonMichelle M Le BeauWendy StockOlaf HeidenreichAbrar AlharbiDavid John AllsupRichard S HoulstonJean NordenAnne M DickinsonElisabeth DouglasBeverley Clare LendremAnn K DalyLouise PalmKim PiechockiSally JeffriesMartin BornhäuserChristoph RölligHeidi AltmannLeo RuhnkeDesiree KunadtLisa WagenführHeather J CordellRebecca DarlayMette K AndersenMaria C FontanaGiovanni MartinelliGiovanni MarconiMiguel Angel SanzJosé CerveraInés Gómez-SeguíThomas CluzeauChimène MoreilhonSophie RaynaudHeinz SillMaria Teresa Teresa VosoFrancesco Lo-CocoHervé DombretMeyling H CheokClaude PreudhommeRosemary E GaleDavid LinchJulia Gaal-WesingerAndras MassziDaniel NowakWolf-Karsten HofmannAmanda GilkesKimmo PorkkaJelena D Milosevic FeenstraRobert KralovicsDavid GrimwadeManja MeggendorferTorsten HaferlachSzilvia KrizsánCsaba BödörFriedrich StölzelKenan OnelJames M AllanPublished in: Nature communications (2021)
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).