Polygenic risk modeling for prediction of epithelial ovarian cancer risk.
Eileen O DarengJonathan P TyrerDaniel R BarnesMichelle R JonesXin YangKatja K H AbenMuriel A AdankSimona AgataIrene L AndrulisHoda Anton-CulverNatalia N AntonenkovaGerasimos AravantinosBanu K ArunAnnelie AugustinssonJudith BalmañaElisa V BanderaRosa B BarkardottirDaniel BarrowdaleMatthias W BeckmannAlicia Beeghly-FadielJavier BenitezMarina BermishevaMarcus Q BernardiniLine BjorgeAmanda BlackNatalia V BogdanovaBernardo BonanniAke BorgJames D BrentonAgnieszka BudzilowskaRalf BützowSaundra S BuysHui CaiMaria A CaligoIan G CampbellRikki CanniotoHayley CassinghamJenny Chang-ClaudeStephen J ChanockKexin ChenYoke-Eng ChiewWendy K ChungKathleen B M ClaesSarah Colonnanull nullnull nullnull nullLinda S CookFergus J CouchMary B DalyFanny DaoEleanor DaviesMiguel de la HoyaRobin de PutterJoe G DennisAllison DePersiaPeter DevileeOrland DiezYuan Chun DingJennifer A DohertySusan M DomchekThilo DörkAndreas du BoisMatthias DürstDiana M EcclesHeather A EliassenChristoph EngelGareth D EvansPeter A FaschingJames M FlanaganRenée T FortnerEva MacháčkováEitan FriedmanPatricia A GanzJudy GarberFrancesca GensiniGraham G GilesGord GlendonAndrew K GodwinMarc T GoodmanMark H GreeneJacek Gronwaldnull nullnull nullEric HahnenChristopher A HaimanNiclas HåkanssonUte HamannThomas V O HansenHolly R HarrisMikael HartmanFlorian HeitzMichelle A T HildebrandtEstrid HøgdallClaus K HøgdallJohn L HopperRuea-Yea HuangChad HuffPeter J HulickDavid G HuntsmanEvgeny N Imyanitovnull nullnull nullClaudine IsaacsAnna JakubowskaPaul A JamesRamunas JanaviciusAllan JensenOskar Th JohannssonEsther M JohnMichael E JonesDaehee KangBeth Y KarlanAnthony KarnezisLinda E KelemenElza KhusnutdinovaLambertus A L M KiemeneyByoung-Gie KimSusanne K KjaerIan KomenakaJolanta KupryjanczykAllison W KurianAva KwongDiether LambrechtsMelissa C LarsonConxi Lazaro GarciaNhu D LeGoska LeslieJenny LesterFabienne LesueurDouglas A LevineLian LiJingmei LiJennifer T LoudKaren H LuJan LubińskiPhuong L MaiSiranoush ManoukianJeffrey R MarksRayna Kim MatsunoKeitaro MatsuoTaymaa MayLesley McGuffogJohn R McLaughlinIain A McNeishNoura MebiroukUsha MenonAustin MillerJonathan BeesleyAlbina MinlikeevaFrancesmary ModugnoMarco MontagnaKirsten B MoysichElizabeth MunroKatherine L NathansonSusan L NeuhausenHeli NevanlinnaJoanne Ngeow Yuen YieHenriette Roed NielsenFinn C NielsenLiene Nikitina-ZakeKunle OdunsiKenneth OffitEdith OlahSiel OlbrechtOlufunmilayo I OlopadeSara H OlsonHåkan OlssonAna OsorioLaura PapiSue-Kyung ParkMichael T ParsonsHarsha PathakInge Sokilde PedersenAna PeixotoTanja PejovicPedro Perez-SeguraJennifer B PermuthBeth N PeshkinPaolo PeterlongoAnna PiskorzDarya ProkofyevaPaolo RadiceJohanna RantalaMarjorie J RigganHarvey A RischCristina Rodriguez-AntonaEric A RossMary Anne RossingIngo RunnebaumDale R SandlerMarta SantamariñaPenny SoucyRita K SchmutzlerV Wendy SetiawanKang ShanWeiva SiehJacques SimardChristian F SingerAnna P SokolenkoHonglin SongMelissa C SoutheyHelen SteedDominique Stoppat-LyonnetRebecca SutphenAnthony J SwerdlowYen Yen TanManuel R TeixeiraSoo-Hwang TeoKathryn L TerryMary Beth Terrynull nullnull nullMads ThomassenPamela J ThompsonLiv Cecilie Vestrheim ThomsenDarcy L ThullMarc TischkowitzLinda TitusAmanda Ewart TolandDiana TorresBritton TrabertRuth C TravisNadine TungShelley T TworogerEllen ValenAnne M van AltenaAnnemieke H van der HoutEls Van NieuwenhuysenElizabeth J vanRensburgAna VegaDigna Velez EdwardsRobert A VierkantFrances WangBarbara WappenschmidtPenelope M WebbClarice R WeinbergJeffrey N WeitzelNicolas WentzensenEmily WhiteAlice S WhittemoreStacey J WinhamAlicja WolkYin-Ling WooAnna H WuLi YanDrakoulis YannoukakosKatia M ZavagliaWei ZhengArgyrios ZiogasKristin K ZornZdenek KleiblDouglas F EastonKate LawrensonAnna De FazioThomas A SellersSusan J RamusCeleste L PearceAlvaro N A MonteiroJulie M CunninghamEllen L GoodeJoellen M SchildkrautAndrew BerchuckGeorgia Chenevix-TrenchSimon A GaytherAntonis C AntoniouPaul David Peter PharoahPublished in: European journal of human genetics : EJHG (2022)
Polygenic risk scores (PRS) for epithelial ovarian cancer (EOC) have the potential to improve risk stratification. Joint estimation of Single Nucleotide Polymorphism (SNP) effects in models could improve predictive performance over standard approaches of PRS construction. Here, we implemented computationally efficient, penalized, logistic regression models (lasso, elastic net, stepwise) to individual level genotype data and a Bayesian framework with continuous shrinkage, "select and shrink for summary statistics" (S4), to summary level data for epithelial non-mucinous ovarian cancer risk prediction. We developed the models in a dataset consisting of 23,564 non-mucinous EOC cases and 40,138 controls participating in the Ovarian Cancer Association Consortium (OCAC) and validated the best models in three populations of different ancestries: prospective data from 198,101 women of European ancestries; 7,669 women of East Asian ancestries; 1,072 women of African ancestries, and in 18,915 BRCA1 and 12,337 BRCA2 pathogenic variant carriers of European ancestries. In the external validation data, the model with the strongest association for non-mucinous EOC risk derived from the OCAC model development data was the S4 model (27,240 SNPs) with odds ratios (OR) of 1.38 (95% CI: 1.28-1.48, AUC: 0.588) per unit standard deviation, in women of European ancestries; 1.14 (95% CI: 1.08-1.19, AUC: 0.538) in women of East Asian ancestries; 1.38 (95% CI: 1.21-1.58, AUC: 0.593) in women of African ancestries; hazard ratios of 1.36 (95% CI: 1.29-1.43, AUC: 0.592) in BRCA1 pathogenic variant carriers and 1.49 (95% CI: 1.35-1.64, AUC: 0.624) in BRCA2 pathogenic variant carriers. Incorporation of the S4 PRS in risk prediction models for ovarian cancer may have clinical utility in ovarian cancer prevention programs.