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
Included in
Diseases Commons, Genetic Phenomena Commons, Medical Genetics Commons, Public Health Commons