Characterizing prostate cancer risk through multi-ancestry genome-wide discovery of 187 novel risk variants.
Anqi WangJiayi ShenAlex A RodriguezEdward J SaundersFei ChenRohini JanivaraBurcu F DarstXin ShengYili XuAlisha J ChouSara BenllochTokhir DadaevMark N BrookAnna PlymAli SahimiThomas J HoffmannAtsushi TakahashiKoichi MatsudaYukihide MomozawaMasashi FujitaTriin LaiskJéssica FiguerêdoKenneth Ross MuirShuji ItoXiaoxi Liunull nullYuji UchioMichiaki KuboYoichiro KamataniArtitaya LophatananonPeggy WanCaroline AndrewsAdriana LoriParichoy P ChoudhuryJohanna SchleutkerTeuvo L J TammelaCsilla SipekyAnssi AuvinenGraham G GilesMelissa C SoutheyRobert J MacInnisCezary CybulskiDominika WokolorczykJan LubinskiChristopher T RentschKelly ChoBenjamin H McmahonDavid E NealJenny L DonovanFreddie C HamdyRichard M MartinBørge Grønne NordestgaardSune F NielsenMaren WeischerStig Egil BojesenMartin Andreas RøderHein Vincent StroombergJyotsna BatraSuzanne ChambersLisa G HorvathJudith A ClementsWayne D TilleyGail P RisbridgerHenrik GronbergMarkus AlyRobert SzulkinMartin EklundTobias NordströmNora PashayanAlison M DunningMaya GhoussainiRuth C TravisTim J KeyElio RiboliJong Y ParkThomas A SellersHui-Yi LinDemetrios AlbanesStephanie J WeinsteinMichael B CookLorelei A MucciEdward GiovannucciSara LindstromPeter KraftDavid J HunterKathryn L PenneyConstance TurmanCatherine M TangenPhyllis J GoodmanIan M ThompsonRobert J HamiltonNeil E FleshnerAntonio FinelliMarie-Elise ParentJanet L StanfordElaine A OstranderStella KoutrosLaura E Beane FreemanMeir StampferAlicja WolkNiclas HåkanssonGerald L AndrioleRobert N HooverMitchell J MachielaKarina Dalsgaard SørensenMichael BorreWilliam J BlotQuan LongEdward D YeboahJames Edward MensahYong-Jie LuHong-Wei ZhangNinghan FengXueying MaoYudong WuShan-Chao ZhaoZan SunStephen N ThibodeauShannon K McDonnellDaniel J SchaidCatharine M L WestGill BarnettChristiane MaierThomas SchnoellerManuel LuedekeAdam S KibelBettina F DrakeOlivier CussenotGeraldine Cancel-TassinFlorence MenegauxThérèse TruongYves Akoli KoudouEsther M JohnEli Marie GrindedalLovise MaehleKay-Tee KhawSue A InglesMariana C SternAna VegaAntonio Gómez-CaamañoLaura FachalBarry S RosensteinSarah L KernsHarry OstrerManuel R TeixeiraPaula PauloAndreia BrandãoStephen WatyaAlexander LubwamaJeannette T BensenEbonee N ButlerJames L MohlerJack A TaylorManolis KogevinasTrinidad Dierssen-SotosGemma Castaño-VinyalsLisa Anne Cannon-AlbrightCraig C TeerlinkChad D HuffPatrick PilieYao YuRyan J BohlenderJian GuSara S StromLuc MultignerPascal BlanchetLaurent BrureauRadka KanevaChavdar SlavovVanio MitevRobin J LeachHermann BrennerXuechen ChenBernd HolleczekBen SchöttkerEric E KleinAnn W HsingRick A KittlesBernice OforiChristopher L LogothetisJeri KimSusan L NeuhausenLinda SteeleYuan Chun DingWilliam B IsaacsBarbara NemesureAnselm J M HennisJohn CarptenHardev PandhaAgnieszka MichaelKim De RuyckGert De MeerleerPiet OstJianfeng XuAzad RazackJasmine LimSoo-Hwang TeoLisa F NewcombDaniel W LinJay H FowkeChristine M Neslund-DudasBenjamin A RybickiMarija GamulinDavor LesselTomislav KulisNawaid UsmaniAswin AbrahamSandeep SinghalMatthew ParliamentFrank ClaessensSteven JoniauThomas Van den BroeckManuela Gago-DominguezJose Esteban CastelaoMaria Elena MartinezSamantha LarkinPaul A TownsendClaire Aukim-HastieWilliam S BushMelinda C AldrichDana C CrawfordShiv SrivastavaJennifer CullenGyorgy PetrovicsGraham CaseyYing WangYao TetteyJoseph LachanceWei TangRichard B BiritwumAndrew A AdjeiEvelyn TayAnn TrueloveShelley NiwaKosj YamoahKoveela GovindasamiAnand P ChokkalingamJacob M KeatonJacklyn N HellwegePeter E ClarkMohamed JallohSerigne M GueyeLamine NiangOlufemi OgunbiyiOlayiwola ShittuOlukemi AmoduAkindele O AdebiyiOseremen I Aisuodionoe-ShadrachHafees O AjibolaMustapha A JamdaOlabode P OluwoleMaxwell NwegbuBen AduseiSunny ManteAfua Darkwa-AbrahamsHalimatou DiopSusan M GundellMonique J RoobolGuido W JensterRon H N van SchaikJennifer J HuMaureen SandersonLinda KachuriRohit VarmaRoberta McKean-CowdinMina TorresMichael H PreussRuth J F LoosMatthew ZawistowskiSebastian ZöllnerZeyun LuStephen K Van den EedenDouglas F EastonStefan AmbsTodd L EdwardsReedik MägiTimothy R RebbeckLars G FritscheStephen J ChanockSonja I BerndtFredrik WiklundHidewaki NakagawaJohn S WitteJ Michael GazianoAmy C JusticeNicholas MancusoChikashi C TeraoRosalind A EelesZSofia Kote-JaraiRavi K MadduriDavid V ContiChristopher A HaimanPublished in: Nature genetics (2023)
The transferability and clinical value of genetic risk scores (GRSs) across populations remain limited due to an imbalance in genetic studies across ancestrally diverse populations. Here we conducted a multi-ancestry genome-wide association study of 156,319 prostate cancer cases and 788,443 controls of European, African, Asian and Hispanic men, reflecting a 57% increase in the number of non-European cases over previous prostate cancer genome-wide association studies. We identified 187 novel risk variants for prostate cancer, increasing the total number of risk variants to 451. An externally replicated multi-ancestry GRS was associated with risk that ranged from 1.8 (per standard deviation) in African ancestry men to 2.2 in European ancestry men. The GRS was associated with a greater risk of aggressive versus non-aggressive disease in men of African ancestry (P = 0.03). Our study presents novel prostate cancer susceptibility loci and a GRS with effective risk stratification across ancestry groups.