biostudies-literatureUnknownWeinstock JSNHLBI NIH HHSNIGMS NIH HHSClonal hematopoiesis (CH) is defined by the expansion of a lineage of genetically identical cells in blood. Genetic lesions that confer a fitness advantage, such as point mutations or mosaic chromosomal alterations (mCAs) in genes associated with hematologic malignancy, are frequent mediators of CH. However, recent analyses of both single cell-derived colonies of hematopoietic cells and population sequencing cohorts have revealed CH frequently occurs in the absence of known driver genetic lesions. To characterize CH without known driver genetic lesions, we used 51,399 deeply sequenced whole genomes from the NHLBI TOPMed sequencing initiative to perform simultaneous germline and somatic mutation analyses among individuals without leukemogenic point mutations (LPM), which we term CH-LPMneg. medRxiv : the preprint server for health sciences2024.08.22.24312319https://www.ebi.ac.uk/biostudies/studies/S-EPMC11370504biostudies-literatureThe Genetic Determinants and Genomic Consequences of Non-Leukemogenic Somatic Point Mutations.PMC11370504U01 HL120393HHSN268201800001CK08 HL166690R01 HL120393R01 HL117626R35 GM139580R01 HL105756Psaty BMMathias RKarantanos TRotter JILaurie CChami NGuo XO'Brien EBoerwinkle EAbecasis GRRich SSSankaran VWeinstock JSLowenstein CJNassir RJakubek YATracy RPKang HMBroome JGVasan RSLoos RJRaffield LMReiner ABattle AKenny EEGu CCCho MHBrody JAIoannou MPeyser PAHaring BKardia SLLiggett LAChaudhry SARussell TPBidulescu AScheet PHsiung CAde Andrade MSmith AVPost WSSmith JANatarajan PTaylor KDReventun PBlackwell TWArvanitis MBick AKhan AYun JHJaiswal SKooperberg CViskadourou MChen YIAuer PfalseThe Genetic Determinants and Genomic Consequences of Non-Leukemogenic Somatic Point Mutations.Clonal hematopoiesis (CH) is defined by the expansion of a lineage of genetically identical cells in blood. Genetic lesions that confer a fitness advantage, such as point mutations or mosaic chromosomal alterations (mCAs) in genes associated with hematologic malignancy, are frequent mediators of CH. However, recent analyses of both single cell-derived colonies of hematopoietic cells and population sequencing cohorts have revealed CH frequently occurs in the absence of known driver genetic lesions. To characterize CH without known driver genetic lesions, we used 51,399 deeply sequenced whole genomes from the NHLBI TOPMed sequencing initiative to perform simultaneous germline and somatic mutation analyses among individuals without leukemogenic point mutations (LPM), which we term CH-LPMneg. 2024-01-01T00:00:00Z2024 Aug2026-07-14T10:19:39.485Z2025-04-04T00:29:25.338ZS-EPMC113705043922873710.1101/2024.08.22.24312319