Insights into clonal haematopoiesis from 8,342 mosaic chromosomal alterations Journal Article


Authors: Loh, P. R.; Genovese, G.; Handsaker, R. E.; Finucane, H. K.; Reshef, Y. A.; Palamara, P. F.; Birmann, B. M.; Talkowski, M. E.; Bakhoum, S. F.; McCarroll, S. A.; Price, A. L.
Article Title: Insights into clonal haematopoiesis from 8,342 mosaic chromosomal alterations
Abstract: The selective pressures that shape clonal evolution in healthy individuals are largely unknown. Here we investigate 8,342 mosaic chromosomal alterations, from 50 kb to 249 Mb long, that we uncovered in blood-derived DNA from 151,202 UK Biobank participants using phase-based computational techniques (estimated false discovery rate, 6-9%). We found six loci at which inherited variants associated strongly with the acquisition of deletions or loss of heterozygosity in cis. At three such loci (MPL, TM2D3-TARSL2, and FRA10B), we identified a likely causal variant that acted with high penetrance (5-50%). Inherited alleles at one locus appeared to affect the probability of somatic mutation, and at three other loci to be objects of positive or negative clonal selection. Several specific mosaic chromosomal alterations were strongly associated with future haematological malignancies. Our results reveal a multitude of paths towards clonal expansions with a wide range of effects on human health. © 2018 Macmillan Publishers Ltd., part of Springer Nature.
Journal Title: Nature
Volume: 559
Issue: 7714
ISSN: 0028-0836
Publisher: Nature Publishing Group  
Date Published: 2018-07-19
Start Page: 350
End Page: 355
Language: English
DOI: 10.1038/s41586-018-0321-x
PROVIDER: scopus
PMCID: PMC6054542
PUBMED: 29995854
DOI/URL:
Notes: Article -- Export Date: 1 August 2018 -- Source: Scopus
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MSK Authors
  1. Samuel F Bakhoum
    17 Bakhoum