Combining Asian and European genome-wide association studies of colorectal cancer improves risk prediction across racial and ethnic populations.
Minta ThomasYu-Ru SuElisabeth A RosenthalLori C SakodaStephanie L SchmitMaria N TimofeevaZhishan ChenCeres Fernández-RozadillaPhilip J LawNeil MurphyRobert Carreras-TorresVirginia Diez-ObreroFranzel J B van DuijnhovenShangqing JiangAesun ShinAlicja WolkAmanda I PhippsAndrea Burnett-HartmanAndrea GsurAndrew T ChanAnn G ZauberAnna H WuAnnika LindblomCaroline Y UmCatherine M TangenChristopher R GignouxChristina NewtonChristopher A HaimanConghui QuD Timothy Timothy BishopDaniel D BuchananDavid R CrosslinDavid V ContiDong-Hyun KimElizabeth HauserEmily WhiteErin M SiegelFredrick R SchumacherGadi RennertGraham G GilesHeather HampelHermann BrennerIsao OzeJae Hwan OhJeffrey K LeeJennifer L SchneiderJenny Chang-ClaudeJeong-Seon KimJeroen R HuygheJiayin ZhengJochen HampeJoel GreensonJohn L HopperJulie R PalmerKala VisvanathanKeitaro MatsuoKoichi MatsudaKeum Ji JungLi LiLoic Le MarchandLudmila VodickovaLuis BujandaMarc J GunterMarco MatejcicMark E JenkinsMartha L SlatteryMauro D'AmatoMeilin WangMichael HoffmeisterMichael O WoodsMichelle KimMingyang SongMotoki IwasakiMulong DuNatalia UdaltsovaNorie SawadaPavel VodickaPeter T CampbellPolly A NewcombQiuyin CaiRachel PearlmanRish K PaiRobert E SchoenRobert S SteinfelderRobert W HaileRosita VandenputtelaarRoss L PrenticeSébastien KürySergi Castellví-BelShoichiro TsuganeSonja I BerndtSoo Chin LeeStefanie BrezinaStephanie J WeinsteinStephen J ChanockSun Ha JeeSun-Seog KweonSusan VadaparampilTabitha A HarrisonTaiki YamajiTemitope O KekuVeronika VymetalkovaVolker ArndtWei-Hua JiaXiao-Ou ShuYi LinYoon-Ok AhnZsofia K StadlerBethany Van GuelpenCornelia M UlrichElizabeth A PlatzJohn D PotterChristopher I LiReinier MeesterVictor MorenoJane C FigueiredoGraham CaseyIris Lansdorp VogelaarMalcolm G DunlopStephen B GruberRichard B HayesPaul David Peter PharoahRichard S HoulstonGail P JarvikIan P M TomlinsonQuan LongDouglas A CorleyUlrike PetersLi HsuPublished in: Nature communications (2023)
Polygenic risk scores (PRS) have great potential to guide precision colorectal cancer (CRC) prevention by identifying those at higher risk to undertake targeted screening. However, current PRS using European ancestry data have sub-optimal performance in non-European ancestry populations, limiting their utility among these populations. Towards addressing this deficiency, we expand PRS development for CRC by incorporating Asian ancestry data (21,731 cases; 47,444 controls) into European ancestry training datasets (78,473 cases; 107,143 controls). The AUC estimates (95% CI) of PRS are 0.63(0.62-0.64), 0.59(0.57-0.61), 0.62(0.60-0.63), and 0.65(0.63-0.66) in independent datasets including 1681-3651 cases and 8696-115,105 controls of Asian, Black/African American, Latinx/Hispanic, and non-Hispanic White, respectively. They are significantly better than the European-centric PRS in all four major US racial and ethnic groups (p-values < 0.05). Further inclusion of non-European ancestry populations, especially Black/African American and Latinx/Hispanic, is needed to improve the risk prediction and enhance equity in applying PRS in clinical practice.