Differences in polygenic score distributions in European ancestry populations: implications for breast cancer risk prediction.
Kristia YiangouNasim MavaddatJoe DennisMaria ZantiQin WangManjeet K BollaMustapha AbubakarThomas U AhearnIrene L AndrulisHoda Anton-CulverNatalia N AntonenkovaVolker ArndtKristan J AronsonAnnelie AugustinssonAdinda BatenSabine BehrensMarina BermishevaAmy Berrington de GonzalezKatarzyna BiałkowskaNicholas BoddickerClara BodelonNatalia V BogdanovaStig E BojesenKristen D BrantleyHiltrud BrauchHermann BrennerNicola J CampFederico CanzianJose E CastelaoMelissa H CessnaJenny Chang-ClaudeGeorgia Chenevix-TrenchWendy K Chungnull nullSarah V ColonnaFergus J CouchAngela CoxSimon S CrossKamila CzeneMary B DalyPeter DevileeThilo DörkAlison M DunningDiana M EcclesA Heather EliassenChristoph EngelMikael ErikssonD Gareth EvansPeter A FaschingOlivia FletcherHenrik FlygerLin FritschiManuela Gago-DominguezAleksandra Gentry-MaharajAnna González-NeiraPascal GuénelEric HahnenChristopher A HaimanUte HamannJaana M HartikainenVikki HoJames HodgeAntoinette HollestelleEllen HonischMaartje J HooningReiner HoppeJohn L HopperSacha HowellAnthony Howellnull nullnull nullSimona JakovchevskaAnna JakubowskaHelena JernströmNichola JohnsonRudolf KaaksElza K KhusnutdinovaCari M KitaharaStella KoutrosVessela N KristensenJames V LaceyDiether LambrechtsFlavio LejbkowiczAnnika LindblomMichael LushArto MannermaaDimitrios MavroudisUsha MenonRachel A MurphyHeli NevanlinnaNadia ObiKenneth OffitTjoung-Won Park-SimonAlpa V PatelCheng PengPaolo PeterlongoGuillermo PitaDijana Plaseska-KaranfilskaKatri PylkäsPaolo RadiceMuhammad U RashidGadi RennertEleanor RobertsJuan RodriguezAtocha RomeroEfraim H RosenbergEmmanouil SaloustrosDale P SandlerElinor J SawyerRita K SchmutzlerChristopher G ScottXiao-Ou ShuMelissa C SoutheyJennifer StoneJack A TaylorLauren R TerasIrma van de BeekWalter WillettRobert WinqvistWei ZhengCeline M VachonMarjanka K SchmidtPer HallRobert J MacInnisRoger L MilnePaul D P PharoahJacques SimardAntonis C AntoniouDouglas F EastonKyriaki MichailidouPublished in: medRxiv : the preprint server for health sciences (2024)
The 313-variant polygenic risk score (PRS 313 ) provides a promising tool for breast cancer risk prediction. However, evaluation of the PRS 313 across different European populations which could influence risk estimation has not been performed. Here, we explored the distribution of PRS 313 across European populations using genotype data from 94,072 females without breast cancer, of European-ancestry from 21 countries participating in the Breast Cancer Association Consortium (BCAC) and 225,105 female participants from the UK Biobank. The mean PRS 313 differed markedly across European countries, being highest in south-eastern Europe and lowest in north-western Europe. Using the overall European PRS 313 distribution to categorise individuals leads to overestimation and underestimation of risk in some individuals from south-eastern and north-western countries, respectively. Adjustment for principal components explained most of the observed heterogeneity in mean PRS. Country-specific PRS distributions may be used to calibrate risk categories in individuals from different countries.