Faculty, Staff and Student Publications

Publication Date

4-28-2023

Journal

Science Advances

Abstract

Nononcogenic somatic mutations are thought to be uncommon and inconsequential. To test this, we analyzed 43,693 National Heart, Lung and Blood Institute Trans-Omics for Precision Medicine blood whole genomes from 37 cohorts and identified 7131 non-missense somatic mutations that are recurrently mutated in at least 50 individuals. These recurrent non-missense somatic mutations (RNMSMs) are not clearly explained by other clonal phenomena such as clonal hematopoiesis. RNMSM prevalence increased with age, with an average 50-year-old having 27 RNMSMs. Inherited germline variation associated with RNMSM acquisition. These variants were found in genes involved in adaptive immune function, proinflammatory cytokine production, and lymphoid lineage commitment. In addition, the presence of eight specific RNMSMs associated with blood cell traits at effect sizes comparable to Mendelian genetic mutations. Overall, we found that somatic mutations in blood are an unexpectedly common phenomenon with ancestry-specific determinants and human health consequences.

Keywords

Humans, Middle Aged, Hematopoiesis, Mutation, Germ-Line Mutation, Mutation, Missense, Phenotype

DOI

10.1126/sciadv.abm4945

PMID

37126548

PMCID

PMC10132750

PubMedCentral® Posted Date

4-26-2023

PubMedCentral® Full Text Version

Post-print

Published Open-Access

yes

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