biostudies-literaturePershad YU.S. Department of Health & Human Services | NIH | National Institute of General Medical SciencesNIDDK NIH HHSNIA NIH HHSU.S. Department of Health & Human Services | NIH | National Institute on AgingNHLBI NIH HHSBurroughs Wellcome Foundation Career Award for Medical ScientistsNIMHD NIH HHSU.S. Department of Health & Human Services | NIH | National Heart, Lung, and Blood InstituteNIH HHSNIGMS NIH HHS3800https://www.ebi.ac.uk/biostudies/studies/S-EPMC11076528biostudies-literatureUnknown15(1)Clonal hematopoiesis (CH) is characterized by the acquisition of a somatic mutation in a hematopoietic stem cell that results in a clonal expansion. These driver mutations can be single nucleotide variants in cancer driver genes or larger structural rearrangements called mosaic chromosomal alterations (mCAs). The factors that influence the variations in mCA fitness and ultimately result in different clonal expansion rates are not well understood. We used the Passenger-Approximated Clonal Expansion Rate (PACER) method to estimate clonal expansion rate as PACER scores for 6,381 individuals in the NHLBI TOPMed cohort with gain, loss, and copy-neutral loss of heterozygosity mCAs. Our mCA fitness estimates, derived by aggregating per-individual PACER scores, were correlated (R² = 0.4Nature communicationsDeterminants of mosaic chromosomal alteration fitness.PMC11076528R01 DK117445R01 AG083736R01 HL120393R01 HL117626T32 GM007347R01 MD012765U01 HL120393HHSN268201800001CR01AG083736DP5 OD029586T32GM007347DP5OD029586R01 HL105756Arnett DPankratz NPsaty BMRotter JIRoden DMLewis JPChami NJohnson ADGuo XBoerwinkle EDesai PPershad YSilverman EKRich SSDoyle MFLoos RJFWeinstock JSCox NJJakubek YAWang ZScheet PAReiner APBarnes KAuer PLStilp AMRaffield LMShojaie AFranceschini NYun JHRedline SCho MHBis JCMathias RAPoisner HJaiswal STaub MADeMeo DLevy DMack TBick AGFornage MCarson APMitchell BDNorth KEfalseDeterminants of mosaic chromosomal alteration fitness.Clonal hematopoiesis (CH) is characterized by the acquisition of a somatic mutation in a hematopoietic stem cell that results in a clonal expansion. These driver mutations can be single nucleotide variants in cancer driver genes or larger structural rearrangements called mosaic chromosomal alterations (mCAs). The factors that influence the variations in mCA fitness and ultimately result in different clonal expansion rates are not well understood. We used the Passenger-Approximated Clonal Expansion Rate (PACER) method to estimate clonal expansion rate as PACER scores for 6,381 individuals in the NHLBI TOPMed cohort with gain, loss, and copy-neutral loss of heterozygosity mCAs. Our mCA fitness estimates, derived by aggregating per-individual PACER scores, were correlated (R² = 0.42024-01-01T00:00:00Z2024 May2026-06-01T20:15:09.51Z2026-05-20T03:08:36.78ZS-EPMC110765283871470310.1038/s41467-024-48190-8