@article{914f1399a8fd47ec9f2d9cd0e9f144e2,
title = "The genetic determinants of recurrent somatic mutations in 43,693 blood genomes",
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.",
author = "{NHLBI Trans-Omics for Precision Medicine (TOPMed) Consortium} and Weinstock, {Joshua S.} and Laurie, {Cecelia A.} and Broome, {Jai G.} and Taylor, {Kent D.} and Xiuqing Guo and Shuldiner, {Alan R.} and O'Connell, {Jeffrey R.} and Lewis, {Joshua P.} and Eric Boerwinkle and Barnes, {Kathleen C.} and Nathalie Chami and Kenny, {Eimear E.} and Loos, {Ruth J.F.} and Myriam Fornage and Susan Redline and Cade, {Brian E.} and Gilliland, {Frank D.} and Zhanghua Chen and Gauderman, {W. James} and Rajesh Kumar and Leslie Grammer and Schleimer, {Robert P.} and Psaty, {Bruce M.} and Bis, {Joshua C.} and Brody, {Jennifer A.} and Silverman, {Edwin K.} and Yun, {Jeong H.} and Dandi Qiao and Weiss, {Scott T.} and Jessica Lasky-Su and DeMeo, {Dawn L.} and Palmer, {Nicholette D.} and Freedman, {Barry I.} and Bowden, {Donald W.} and Cho, {Michael H.} and Vasan, {Ramachandran S.} and Johnson, {Andrew D.} and Yanek, {Lisa R.} and Becker, {Lewis C.} and Sharon Kardia and Jiang He and Robert Kaplan and Heckbert, {Susan R.} and Smith, {Nicholas L.} and Wiggins, {Kerri L.} and Arnett, {Donna K.} and Irvin, {Marguerite R.} and Hemant Tiwari and Adolfo Correa and Raffield, {Laura M.}",
note = "Publisher Copyright: Copyright {\textcopyright} 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).",
year = "2023",
month = apr,
doi = "10.1126/SCIADV.ABM4945",
language = "English (US)",
volume = "9",
journal = "Science Advances",
issn = "2375-2548",
publisher = "American Association for the Advancement of Science",
number = "17",
}
