@article {9588,
	title = {Determinants of mosaic chromosomal alteration fitness.},
	journal = {medRxiv},
	year = {2023},
	month = {2023 Oct 21},
	abstract = {<p>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 for 6,381 individuals in the NHLBI TOPMed cohort with gain, loss, and copy-neutral loss of heterozygosity mCAs. Our estimates of mCA fitness were correlated (R  = 0.49) with an alternative approach that estimated fitness of mCAs in the UK Biobank using a theoretical probability distribution. Individuals with lymphoid-associated mCAs had a significantly higher white blood cell count and faster clonal expansion rate. In a cross-sectional analysis, genome-wide association study of estimates of mCA expansion rate identified  ,  , and  locus variants as modulators of mCA clonal expansion rate.</p>},
	doi = {10.1101/2023.10.20.23297280},
	author = {Pershad, Yash and Mack, Taralynn and Poisner, Hannah and Jakubek, Yasminka A and Stilp, Adrienne M and Mitchell, Braxton D and Lewis, Joshua P and Boerwinkle, Eric and Loos, Ruth J and Chami, Nathalie and Wang, Zhe and Barnes, Kathleen and Pankratz, Nathan and Fornage, Myriam and Redline, Susan and Psaty, Bruce M and Bis, Joshua C and Shojaie, Ali and Silverman, Edwin K and Cho, Michael H and Yun, Jeong and DeMeo, Dawn and Levy, Daniel and Johnson, Andrew and Mathias, Rasika and Taub, Margaret and Arnett, Donna and North, Kari and Raffield, Laura M and Carson, April and Doyle, Margaret F and Rich, Stephen S and Rotter, Jerome I and Guo, Xiuqing and Cox, Nancy and Roden, Dan M and Franceschini, Nora and Desai, Pinkal and Reiner, Alex and Auer, Paul L and Scheet, Paul and Jaiswal, Siddhartha and Weinstock, Joshua S and Bick, Alexander G}
}
