ArticleScience advances2023
The genetic determinants of recurrent somatic mutations in 43,693 blood genomes.
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Article in Science advances, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers.
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8citing papers in PubMed
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Who cites it
8 citing papers in PubMed.
- Genomic Perspective on Heterogeneity of Organs and Body Aging.Aging cell · 2026Review
- Genetic determinants and genomic consequences of non-leukemogenic somatic point mutations.Nature communications · 2025Article
- Monitoring the rate and variability of somatic genomic alterations using long-read sequencing.Scientific reports · 2025Article
- A genotype-first approach identifies high incidence of NF1 pathogenic variants with distinct disease associations.Nature communications · 2025Article
- Pathogenesis and inflammaging in myelodysplastic syndrome.Haematologica · 2025Review
- A modeling of complex trait phenotypic variance determinants.PNAS nexus · 2024Article
- The Genetic Determinants and Genomic Consequences of Non-Leukemogenic Somatic Point Mutations.medRxiv : the preprint server for health sciences · 2024Article
- Genetic variation across and within individuals.Nature reviews. Genetics · 2024Review
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Authors and funding
88 authors.
Joshua S WeinstockCenter for Statistical Genetics, Department of Biostatistics, University of Michigan School of Public Health, Ann Arbor, MI 48109, USA.ORCID 0000-0001-7013-1899
Cecelia A LaurieDepartment of Biostatistics, University of Washington, Seattle, WA 98195, USA.
Jai G BroomeDepartment of Biostatistics, University of Washington, Seattle, WA 98195, USA.ORCID 0000-0001-7638-0749
Kent D TaylorThe Institute for Translational Genomics and Population Sciences, Department of Pediatrics, The Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center, Torrance, CA 90502, USA.ORCID 0000-0002-2756-4370
Xiuqing GuoThe Institute for Translational Genomics and Population Sciences, Department of Pediatrics, The Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center, Torrance, CA 90502, USA.ORCID 0000-0002-5264-5068
Alan R ShuldinerDepartment of Medicine, University of Maryland, Baltimore, Baltimore, MD 21201, USA.ORCID 0000-0001-9921-4305
Jeffrey R O'ConnellDepartment of Medicine, University of Maryland, Baltimore, Baltimore, MD 21201, USA.
Joshua P LewisDepartment of Medicine, University of Maryland, Baltimore, Baltimore, MD 21201, USA.ORCID 0000-0002-4107-6066
Eric BoerwinkleHuman Genome Sequencing Center, Baylor College of Medicine, Houston, TX 77030, USA.
Kathleen C BarnesDivision of Biomedical Informatics and Personalized Medicine, Department of Medicine, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA.
Nathalie ChamiThe Charles Bronfman Institute of Personalized Medicine, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.ORCID 0000-0002-8547-6424
Eimear E KennyInstitute for Genomic Health, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.ORCID 0000-0001-9198-759X
Ruth J F LoosThe Charles Bronfman Institute of Personalized Medicine, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.ORCID 0000-0002-8532-5087
Myriam FornageBrown Foundation Institute of Molecular Medicine, McGovern Medical School, University of Texas Health Science Center at Houston, Houston, TX 77030, USA.ORCID 0000-0003-0677-8158
Susan RedlineDepartment of Medicine, Brigham and Women's Hospital, Boston, MA 02115, USA.ORCID 0000-0002-6585-1610
Brian E CadeDepartment of Medicine, Brigham and Women's Hospital, Boston, MA 02115, USA.ORCID 0000-0003-1424-0673
Frank D GillilandDepartment of Preventive Medicine, University of Southern California, Los Angeles, CA 90089, USA.
Zhanghua ChenDepartment of Preventive Medicine, University of Southern California, Los Angeles, CA 90089, USA.
W James GaudermanDepartment of Preventive Medicine, University of Southern California, Los Angeles, CA 90089, USA.ORCID 0000-0002-6626-9091
Rajesh KumarAnn and Robert H. Lurie Children's Hospital of Chicago, Chicago, IL 60611, USA.
Leslie GrammerNorthwestern University Feinberg School of Medicine, Chicago, IL 60611, USA.ORCID 0000-0001-6860-2014
Robert P SchleimerNorthwestern University Feinberg School of Medicine, Chicago, IL 60611, USA.ORCID 0000-0002-8330-0097
Bruce M PsatyCardiovascular Health Research Unit, Department of Medicine, University of Washington, Seattle, WA 98195, USA.
Joshua C BisCardiovascular Health Research Unit, Department of Medicine, University of Washington, Seattle, WA 98195, USA.ORCID 0000-0002-3409-1110
Jennifer A BrodyCardiovascular Health Research Unit, Department of Medicine, University of Washington, Seattle, WA 98195, USA.ORCID 0000-0001-8509-148X
Edwin K SilvermanChanning Division of Network Medicine, Brigham and Women's Hospital, Boston, MA 02115, USA.ORCID 0000-0002-3641-3822
Jeong H YunChanning Division of Network Medicine, Brigham and Women's Hospital, Boston, MA 02115, USA.ORCID 0000-0002-4361-8295
Dandi QiaoChanning Division of Network Medicine, Brigham and Women's Hospital, Boston, MA 02115, USA.ORCID 0000-0001-9450-205X
Scott T WeissDepartment of Medicine, Brigham and Women's Hospital, Boston, MA 02115, USA.ORCID 0000-0001-7196-303X
Jessica Lasky-SuDepartment of Medicine, Brigham and Women's Hospital, Boston, MA 02115, USA.
Dawn L DeMeoDepartment of Medicine, Brigham and Women's Hospital, Boston, MA 02115, USA.
Nicholette D PalmerDepartment of Biochemistry, Wake Forest School of Medicine, Winston-Salem, NC 27101, USA.ORCID 0000-0001-8883-2511
Barry I FreedmanDepartment of Internal Medicine, Section on Nephrology, Wake Forest School of Medicine, Winston-Salem, NC 27101, USA.ORCID 0000-0003-0275-5530
Donald W BowdenDepartment of Biochemistry, Wake Forest School of Medicine, Winston-Salem, NC 27101, USA.
Michael H ChoChanning Division of Network Medicine and Division of Pulmonary and Critical Care Medicine, Brigham and Women's Hospital, Boston, MA 02115, USA.ORCID 0000-0002-4907-1657
Ramachandran S VasanNational Heart, Lung, and Blood Institute's, Boston University's Framingham Heart Study, Framingham, MA 01701, USA.ORCID 0000-0001-7357-5970
Andrew D JohnsonNational Heart, Lung, and Blood Institute's, Boston University's Framingham Heart Study, Framingham, MA 01701, USA.ORCID 0000-0001-6369-5178
Lisa R YanekDepartment of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.ORCID 0000-0001-7117-1075
Lewis C BeckerDepartment of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.ORCID 0000-0003-4805-3403
Sharon KardiaDepartment of Epidemiology, School of Public Health, University of Michigan, Ann Arbor, MI 48109, USA.
Jiang HeDepartment of Epidemiology, Tulane University School of Public Health and Tropical Medicine, New Orleans, LA 70112, USA.ORCID 0000-0002-8286-9652
Robert KaplanDepartment of Epidemiology and Population Health, Albert Einstein College of Medicine, Bronx, NY 10461, USA.
Susan R HeckbertDepartment of Epidemiology, University of Washington, Seattle, WA 98195, USA.ORCID 0000-0002-7100-512X
Nicholas L SmithDepartment of Epidemiology, University of Washington, Seattle, WA 98195, USA.
Kerri L WigginsCardiovascular Health Research Unit, Department of Medicine, University of Washington, Seattle, WA 98101, USA.ORCID 0000-0003-2749-1279
Donna K ArnettDean's Office, College of Public Health, University of Kentucky, Lexington, KY 40506, USA.ORCID 0000-0003-2219-657X
Marguerite R IrvinUniversity of Alabama at Birmingham, Birmingham, AL 35294, USA.
Hemant TiwariUniversity of Alabama at Birmingham, Birmingham, AL 35294, USA.
Adolfo CorreaDepartment of Medicine, Jackson Heart Study, University of Mississippi Medical Center, Jackson, MS 39216, USA.ORCID 0000-0002-9501-600X
Laura M RaffieldDepartment of Genetics, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.ORCID 0000-0002-7892-193X
Yan GaoDepartment of Medicine, University of Mississippi Medical Center, Jackson, MS 39216, USA.ORCID 0000-0002-2901-6933
Mariza de AndradeDepartment of Health Sciences Research, Mayo Clinic, Rochester, MN 55905, USA.
Jerome I RotterThe Institute for Translational Genomics and Population Sciences, Department of Pediatrics, The Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center, Torrance, CA 90502, USA.ORCID 0000-0001-7191-1723
Stephen S RichDepartment of Public Health Sciences, Center for Public Health Genomics, University of Virginia, Charlottesville, VA 22903, USA.ORCID 0000-0003-3872-7793
Ani W ManichaikulDepartment of Public Health Sciences, Center for Public Health Genomics, University of Virginia, Charlottesville, VA 22903, USA.ORCID 0000-0002-5998-795X
Barbara A KonkleDepartment of Medicine, University of Washington, Seattle, WA 98195, USA.ORCID 0000-0002-3959-8797
Jill M JohnsenDepartment of Medicine, University of Washington, Seattle, WA 98195, USA.ORCID 0000-0002-2279-2550
Marsha M WheelerGenome Science, University of Washington, Seattle, WA 98195, USA.
Brian S CusterVitalant Research Institute, San Francisco, CA 94105, USA.ORCID 0000-0001-6251-366X
Ravindranath DuggiralaDepartment of Human Genetics, University of Texas Rio Grande Valley School of Medicine, Brownsville, TX 78520, USA.ORCID 0000-0003-4761-597X
Joanne E CurranDepartment of Human Genetics, University of Texas Rio Grande Valley School of Medicine, Brownsville, TX 78520, USA.ORCID 0000-0002-6898-155X
John BlangeroDepartment of Human Genetics, University of Texas Rio Grande Valley School of Medicine, Brownsville, TX 78520, USA.
Hongsheng GuiCenter for Individualized and Genomic Medicine Research (CIGMA), Henry Ford Health System, Detroit, MI 48202, USA.
Shujie XiaoCenter for Individualized and Genomic Medicine Research (CIGMA), Henry Ford Health System, Detroit, MI 48202, USA.
L Keoki WilliamsCenter for Individualized and Genomic Medicine Research (CIGMA), Henry Ford Health System, Detroit, MI 48202, USA.
Deborah A MeyersDivision of Genetics, Genomics, and Precision Medicine, University of Arizona, Tucson, AZ 85721, USA.
Xingnan LiDepartment of Medicine, University of Arizona, Tucson, AZ 85721, USA.ORCID 0000-0002-1208-8658
Victor OrtegaWake Forest University School of Medicine, Winston-Salem, NC 27101, USA.
Stephen McGarveyDepartment of Epidemiology and International Health Institute, Brown University School of Public Health, Providence, RI 02903, USA.ORCID 0000-0003-1233-6970
C Charles GuDivision of Biostatistics, Washington University School of Medicine, Campus Box 8067, 660 S. Euclid Avenue, St. Louis, MO 63110, USA.ORCID 0000-0002-8527-8145
Yii-Der Ida ChenThe Institute for Translational Genomics and Population Sciences, Department of Pediatrics, The Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center, Torrance, CA 90502, USA.
Wen-Jane LeeDepartment of Medical Research, Taichung Veterans General Hospital, 1650, Sec. 4, Taiwan Boulevard, Taichung City, Taiwan.ORCID 0000-0002-4390-8129
M Benjamin ShoemakerDivision of Cardiology, Vanderbilt University Medical Center, Nashville, TN 37232, USA.
Dawood DarbarDivision of Cardiology, University of Illinois at Chicago, Chicago, IL 60607, USA.ORCID 0000-0002-4103-5977
Dan RodenDepartments of Medicine, Pharmacology, and Biomedical Informatics, Vanderbilt University Medical Center, Nashville, TN 37232, USA.ORCID 0000-0002-6302-0389
Christine AlbertDepartment of Cardiology, Cedars-Sinai, Los Angeles, CA 90048, USA.
Charles KooperbergDivision of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USA.ORCID 0000-0002-7986-8560
Pinkal DesaiDivision of Hematology and Oncology, Weill Cornell Medicine, New York, NY 10065, USA.ORCID 0000-0002-9816-7284
Thomas W BlackwellCenter for Statistical Genetics, Department of Biostatistics, University of Michigan School of Public Health, Ann Arbor, MI 48109, USA.
Goncalo R AbecasisCenter for Statistical Genetics, Department of Biostatistics, University of Michigan School of Public Health, Ann Arbor, MI 48109, USA.
Albert V SmithCenter for Statistical Genetics, Department of Biostatistics, University of Michigan School of Public Health, Ann Arbor, MI 48109, USA.ORCID 0000-0003-1942-5845
Hyun M KangCenter for Statistical Genetics, Department of Biostatistics, University of Michigan School of Public Health, Ann Arbor, MI 48109, USA.ORCID 0000-0002-3631-3979
Rasika MathiasDepartment of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.ORCID 0000-0002-2282-9042
Pradeep NatarajanProgram in Medical and Population Genetics, Broad Institute of Harvard and MIT, Cambridge, MA 02142, USA.ORCID 0000-0001-8402-7435
Siddhartha JaiswalDepartment of Pathology, Stanford University, Stanford, CA 94305, USA.ORCID 0000-0002-9597-0477
Alexander P ReinerDivision of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USA.
Alexander G BickDivision of Genetic Medicine, Department of Medicine, Vanderbilt University, Nashville, TN 37232, USA.ORCID 0000-0001-5824-9595
NHLBI Trans-Omics for Precision Medicine (TOPMed) Consortium
Funding
Statistical Methods for Integrative Genomics in CancerP01CA196569 · NCI · UNIVERSITY OF SOUTHERN CALIFORNIA · PI William JAMES GAUDERMAN · 2016 to 2026
$25.5MSystems Biology of Airway DiseaseP01HL132825 · NHLBI · BRIGHAM AND WOMEN'S HOSPITAL · PI DEMEO, DAWN L · 2016 to 2020
$12.6MStudies of Rare Genetic Variation in the Isolated Population of SardiniaR01HL117626 · NHLBI · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI ABECASIS, GONCALO · 2013 to 2016
$10.5MRare variants and NHLBI traits in deeply phenotyped cohortsR01HL120393 · NHLBI · UNIVERSITY OF WASHINGTON · PI PSATY, BRUCE M, RICE, KENNETH M. · 2014 to 2016
$8.9MWhole Genome Sequencing to Identify Causal Genetic Variants Influencing CVD RiskR01HL113323 · NHLBI · UNIVERSITY OF TEXAS RIO GRANDE VALLEY · PI BLANGERO, JOHN, CURRAN, JOANNE E. · 2012 to 2016
$8.2MRare variants and NHLBI traits in deeply phenotyped cohortsU01HL120393 · NHLBI · UNIVERSITY OF WASHINGTON · PI PSATY, BRUCE M, RICE, KENNETH M. · 2017 to 2018
$5.6MGenetic Epidemiology of Sleep Apnea and Comorbidities in BiobanksR01HL153805 · NHLBI · BRIGHAM AND WOMEN'S HOSPITAL · PI CADE, BRIAN EDMAND · 2021 to 2025
$3.7MMulti-omic studies of asthma severity in an African ancestry populationR01AI132476 · NIAID · UNIVERSITY OF COLORADO DENVER · PI BARNES, KATHLEEN C, MATHIAS, RASIKA ANN · 2018 to 2022
$3.5MClonal hematopoiesis in human aging and diseaseDP2HL157540 · NHLBI · STANFORD UNIVERSITY · PI JAISWAL, SIDDHARTHA · 2020 to 2020
$2.4MTargeting Clonal Hematopoiesis of Indeterminate Potential Using Human GeneticsDP5OD029586 · OD · VANDERBILT UNIVERSITY MEDICAL CENTER · PI BICK, ALEXANDER · 2020 to 2024
$2.3MThe role of COPD genetic risk factor HHIP on lymphocytic inflammationK08HL146972 · NHLBI · BRIGHAM AND WOMEN'S HOSPITAL · PI YUN, JEONG H · 2020 to 2024
$848kNCI NIH HHS P01 CA196569NHLBI NIH HHS DP2 HL157540NHLBI NIH HHS HHSN268201800001CNHLBI NIH HHS K08 HL146972NHLBI NIH HHS P01 HL132825NHLBI NIH HHS R01 HL113323NHLBI NIH HHS R01 HL117626NHLBI NIH HHS R01 HL120393NHLBI NIH HHS R01 HL153805NHLBI NIH HHS U01 HL120393NIAID NIH HHS R01 AI132476NIH HHS DP5 OD029586
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.
Indexed as
Germ-Line MutationHematopoiesisHumansMiddle AgedMutationMutation, MissensePhenotype
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