biostudies-literatureWang XAmerican Heart AssociationNHLBI NIH HHSNIH HHSU.S. Department of Health & Human Services | National Institutes of Health565-570https://www.ebi.ac.uk/biostudies/studies/S-EPMC10524735biostudies-literatureUnknown68(8)All of Us is a biorepository aiming to advance biomedical research by providing various types of data in diverse human populations. Here we present a demonstration project validating the program's genomic data in 98,622 participants. We sought to replicate known genetic associations for three diseases (atrial fibrillation [AF], coronary artery disease, type 2 diabetes [T2D]) and two quantitative traits (height and low-density lipoprotein [LDL]) by conducting common and rare variant analyses. We identified one known risk locus for AF, five loci for T2D, 143 loci for height, and nine loci for LDL. In gene-based burden tests for rare loss-of-function variants, we replicated associations between TTN and AF, GIGYF1 and T2D, ADAMTS17, ACAN, NPR2 and height, APOB, LDLR, PCSK9 and LDL. Our resultsJournal of human geneticsCommon and rare variants associated with cardiometabolic traits across 98,622 whole-genome sequences in the All of Us research program.PMC10524735OT2 OD026548OT2 OD025315OT2 OD025337OT2 OD026549R01HL157635OT2 OD025277OT2 OD02527618SFRN34110082R01 HL139731U24 OD0231211R01HL157635U24 OD023163U2C OD023196OT2 OD026555R01HL139731OT2 OD026554OT2 OD026557OT2 OD026556R01 HL1576351RO1HL092577OT2 OD023205OT2 OD023206R01 HL092577OT2 OD026551OT2 OD026550OT2 OD026553OT2 OD026552U24 OD023176Talavera GARyu JCondon HEllinor PTKim JOhno-Machado LChoi SHVaitinadin NSAll of Us Research ProgramRamirez AWang XMayo KRLubitz SAfalseCommon and rare variants associated with cardiometabolic traits across 98,622 whole-genome sequences in the All of Us research program.All of Us is a biorepository aiming to advance biomedical research by providing various types of data in diverse human populations. Here we present a demonstration project validating the program's genomic data in 98,622 participants. We sought to replicate known genetic associations for three diseases (atrial fibrillation [AF], coronary artery disease, type 2 diabetes [T2D]) and two quantitative traits (height and low-density lipoprotein [LDL]) by conducting common and rare variant analyses. We identified one known risk locus for AF, five loci for T2D, 143 loci for height, and nine loci for LDL. In gene-based burden tests for rare loss-of-function variants, we replicated associations between TTN and AF, GIGYF1 and T2D, ADAMTS17, ACAN, NPR2 and height, APOB, LDLR, PCSK9 and LDL. Our results2023-01-01T00:00:00Z2023 Aug2026-05-29T14:06:09.28Z2025-02-19T00:11:09.286ZS-EPMC105247353707262310.1038/s10038-023-01147-z