biostudies-literatureVenner ENICHD NIH HHSNIH HHS174https://www.ebi.ac.uk/biostudies/studies/S-EPMC10876563biostudies-literatureUnknown7(1)Disparities in data underlying clinical genomic interpretation is an acknowledged problem, but there is a paucity of data demonstrating it. The All of Us Research Program is collecting data including whole-genome sequences, health records, and surveys for at least a million participants with diverse ancestry and access to healthcare, representing one of the largest biomedical research repositories of its kind. Here, we examine pathogenic and likely pathogenic variants that were identified in the All of Us cohort. The European ancestry subgroup showed the highest overall rate of pathogenic variation, with 2.26% of participants having a pathogenic variant. Other ancestry groups had lower rates of pathogenic variation, including 1.62% for the African ancestry group and 1.32% in the Latino/AdmCommunications biologyThe frequency of pathogenic variation in the All of Us cohort reveals ancestry-driven disparities.PMC10876563OT2 OD026555OT2 OD026554OT2 OD026557OT2 OD026556OT2 OD026548OT2 OD025337OT2 OD025315OT2 OD023205OT2 OD023206OT2 OD026549OT2 OD026551OT2 OD026550OT2 OD026553OT2 OD025277OT2 OD025276OT2 OD026552P50 HD103538U24 OD023121U24 OD023176U24 OD023163U2C OD023196Kleiman FPatterson KCooper KFunk GStark LUhrig JNemeskal PGibbs RAClark CThibodeau SWilkins CScherrer JTaylor KFalcon AReiman EEichler ETaylor AReis SWalker KBreeden MJain PTopol EJain NTsao PWatkins PYamazaki KHebbring SJMcCauley JChandrasekaran SMeller RRosser TMinor MWilkerson BLin DMYuan BWinford EFrano ZLevy DObedin-Maliver JGarrett MSitapati ASuver CBartlett LLunn MHalverson SLennon NGreenland PThomas CBegale MRivera NKaushal RTurner BAhsan HSo-Armah CLee BTaitel MPhilippakis AZhou ADaviglus MKarlson EWMarroquin OFein BSawyer STepp RKelley RMalmstrom TGharavi AGAll of Us Research Program InvestigatorsSmith JDCicek MTalavera GMcPherson DKalra DHandberg EHorne LReilly JRehm HReilly GVassy JEdmunds MKlein DColon-Lopez VKalla SEGibbs RMoreno FAMusick AMelo JToledo DIgho-Pemu PO'Connor GTBoerwinkle ECottler LVenner EKheterpal VCarrasquillo OLamarca BTheodorou AAGlazer DStegeman GSkukla SRaveendran SMurphy SNLough CDesa LLEverhart RWang QKorf BGabriel SRandal FCohn EVos MKeogh KBurke JCarlin RRosales LArgos MMayer-Davis ESalgin LDan RodenJohnson CDCMahr TKarnes JHEmpey PESutherland SLewis MJula MJarvik GRico EMGRadhakrishnan ARoss MEMcGovern PMoore-Vogel JAhmedani BIsasi RTinoco DHRoxas-Murray MCuller EHo JMuse EMcKinney JEder MKraft MHaddad AZuchner SLewis BBoschetti ASGrucza RDoheny KAnton-Culver HOkihiro MIsom JWhittle JOhno-Machado LKamyar RFresko YKohane ITopper SWeiss STHolmes BWPagel MEnard KCrook ESmoller JMarshall VWalz JBasford MFarrar-Edwards DBaca-Motes KAschebook-Kilfoy BSimonson WLichtenstein LHarris PMcGee SVisweswaran SParakh KSmith DWheeler MMMakahi EJarmin JDrum CBurnside EShenkman EChen YJTrousdale RHripcsak GHogan WRPeltz-Rauchman CLaras LPSchlueter EfalseThe frequency of pathogenic variation in the All of Us cohort reveals ancestry-driven disparities.Disparities in data underlying clinical genomic interpretation is an acknowledged problem, but there is a paucity of data demonstrating it. The All of Us Research Program is collecting data including whole-genome sequences, health records, and surveys for at least a million participants with diverse ancestry and access to healthcare, representing one of the largest biomedical research repositories of its kind. Here, we examine pathogenic and likely pathogenic variants that were identified in the All of Us cohort. The European ancestry subgroup showed the highest overall rate of pathogenic variation, with 2.26% of participants having a pathogenic variant. Other ancestry groups had lower rates of pathogenic variation, including 1.62% for the African ancestry group and 1.32% in the Latino/Adm2024-01-01T00:00:00Z2024 Feb2026-06-02T22:44:16.632Z2024-10-17T16:43:18.993ZS-EPMC108765633837443410.1038/s42003-023-05708-y