School of Medicine Publications and Presentations
Document Type
Article
Publication Date
4-28-2023
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.
Recommended Citation
Weinstock, J. S., Laurie, C. A., Broome, J. G., Taylor, K. D., Guo, X., Shuldiner, A. R., O'Connell, J. R., Lewis, J. P., Boerwinkle, E., Barnes, K. C., Chami, N., Kenny, E. E., Loos, R. J. F., Fornage, M., Redline, S., Cade, B. E., Gilliland, F. D., Chen, Z., Gauderman, W. J., Kumar, R., … NHLBI Trans-Omics for Precision Medicine (TOPMed) Consortium (2023). The genetic determinants of recurrent somatic mutations in 43,693 blood genomes. Science advances, 9(17), eabm4945. https://doi.org/10.1126/sciadv.abm4945
Creative Commons License
This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License
Publication Title
Science Advances
DOI
10.1126/sciadv.abm4945
Academic Level
faculty
Mentor/PI Department
Office of Human Genetics
Comments
Copyright © 2023 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works. Distributed under a Creative Commons Attribution NonCommercial License 4.0 (CC BY-NC).