The genetic determinants of recurrent somatic mutations in 43,693 blood genomes-Reference-Cited by-同舟云学术

The genetic determinants of recurrent somatic mutations in 43,693 blood genomes

Published:2023-04-28 Issue:17 Volume:9 Page:
ISSN:2375-2548
Container-title:Science Advances
language:en
Short-container-title:Sci. Adv.

Author:

Weinstock Joshua S.¹^ORCID,Laurie Cecelia A.²,Broome Jai G.²³^ORCID,Taylor Kent D.⁴^ORCID,Guo Xiuqing⁴^ORCID,Shuldiner Alan R.⁵^ORCID,O’Connell Jeffrey R.⁵,Lewis Joshua P.⁵^ORCID,Boerwinkle Eric⁶,Barnes Kathleen C.⁷,Chami Nathalie⁸⁹^ORCID,Kenny Eimear E.¹⁰^ORCID,Loos Ruth J. F.⁸⁹^ORCID,Fornage Myriam¹¹^ORCID,Redline Susan¹²¹³^ORCID,Cade Brian E.¹²¹³¹⁴^ORCID,Gilliland Frank D.¹⁵,Chen Zhanghua¹⁵,Gauderman W. James¹⁵^ORCID,Kumar Rajesh¹⁶¹⁷,Grammer Leslie¹⁷^ORCID,Schleimer Robert P.¹⁷^ORCID,Psaty Bruce M.¹⁸¹⁹²⁰,Bis Joshua C.¹⁸^ORCID,Brody Jennifer A.¹⁸^ORCID,Silverman Edwin K.²¹^ORCID,Yun Jeong H.²¹^ORCID,Qiao Dandi²¹^ORCID,Weiss Scott T.¹²²¹^ORCID,Lasky-Su Jessica¹²²¹,DeMeo Dawn L.¹²²¹,Palmer Nicholette D.²²^ORCID,Freedman Barry I.²³^ORCID,Bowden Donald W.²²,Cho Michael H.²⁴^ORCID,Vasan Ramachandran S.²⁵^ORCID,Johnson Andrew D.²⁵²⁶^ORCID,Yanek Lisa R.²⁷^ORCID,Becker Lewis C.²⁷^ORCID,Kardia Sharon²⁸,He Jiang²⁹^ORCID,Kaplan Robert³⁰,Heckbert Susan R.¹⁹³¹^ORCID,Smith Nicholas L.¹⁹³¹³²,Wiggins Kerri L.³³^ORCID,Arnett Donna K.³⁴^ORCID,Irvin Marguerite R.³⁵,Tiwari Hemant³⁵,Correa Adolfo³⁶^ORCID,Raffield Laura M.³⁷^ORCID,Gao Yan³⁸^ORCID,de Andrade Mariza³⁹,Rotter Jerome I.⁴^ORCID,Rich Stephen S.⁴⁰^ORCID,Manichaikul Ani W.⁴⁰^ORCID,Konkle Barbara A.²⁰^ORCID,Johnsen Jill M.²⁰⁴¹^ORCID,Wheeler Marsha M.⁴²,Custer Brian S.⁴³^ORCID,Duggirala Ravindranath⁴⁴⁴⁵^ORCID,Curran Joanne E.⁴⁴⁴⁵^ORCID,Blangero John⁴⁴⁴⁵,Gui Hongsheng⁴⁶⁴⁷,Xiao Shujie⁴⁶⁴⁷,Williams L. Keoki⁴⁶⁴⁷,Meyers Deborah A.⁴⁸,Li Xingnan⁴⁹^ORCID,Ortega Victor⁵⁰,McGarvey Stephen⁵¹^ORCID,Gu C. Charles⁵²^ORCID,Chen Yii-Der Ida⁴,Lee Wen-Jane⁵³^ORCID,Shoemaker M. Benjamin⁵⁴,Darbar Dawood⁵⁵^ORCID,Roden Dan⁵⁶^ORCID,Albert Christine⁵⁷,Kooperberg Charles⁵⁸^ORCID,Desai Pinkal⁵⁹⁶⁰^ORCID,Blackwell Thomas W.¹,Abecasis Goncalo R.¹⁶¹,Smith Albert V.¹^ORCID,Kang Hyun M.¹^ORCID,Mathias Rasika²⁷^ORCID,Natarajan Pradeep¹⁴⁶²⁶³^ORCID,Jaiswal Siddhartha⁶⁴^ORCID,Reiner Alexander P.⁵⁸¹⁹,Bick Alexander G.⁶⁵^ORCID,

Affiliation:

1. Center for Statistical Genetics, Department of Biostatistics, University of Michigan School of Public Health, Ann Arbor, MI 48109, USA.

2. Department of Biostatistics, University of Washington, Seattle, WA 98195, USA.

3. Division of Medical Genetics, Department of Medicine, University of Washington, Seattle, WA 98195, USA.

4. The 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.

5. Department of Medicine, University of Maryland, Baltimore, Baltimore, MD 21201, USA.

6. Human Genome Sequencing Center, Baylor College of Medicine, Houston, TX 77030, USA.

7. Division of Biomedical Informatics and Personalized Medicine, Department of Medicine, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA.

8. The Charles Bronfman Institute of Personalized Medicine, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.

9. The Mindich Child Health and Development Institute, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.

10. Institute for Genomic Health, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.

11. Brown Foundation Institute of Molecular Medicine, McGovern Medical School, University of Texas Health Science Center at Houston, Houston, TX 77030, USA.

12. Department of Medicine, Brigham and Women’s Hospital, Boston, MA 02115, USA.

13. Harvard Medical School, Boston, MA 02115, USA.

14. Program in Medical and Population Genetics, Broad Institute of Harvard and MIT, Cambridge, MA 02142, USA.

15. Department of Preventive Medicine, University of Southern California, Los Angeles, CA 90089, USA.

16. Ann and Robert H. Lurie Children’s Hospital of Chicago, Chicago, IL 60611, USA.

17. Northwestern University Feinberg School of Medicine, Chicago, IL 60611, USA.

18. Cardiovascular Health Research Unit, Department of Medicine, University of Washington, Seattle, WA 98195, USA.

19. Department of Epidemiology, University of Washington, Seattle, WA 98195, USA.

20. Department of Medicine, University of Washington, Seattle, WA 98195, USA.

21. Channing Division of Network Medicine, Brigham and Women’s Hospital, Boston, MA 02115, USA.

22. Department of Biochemistry, Wake Forest School of Medicine, Winston-Salem, NC 27101, USA.

23. Department of Internal Medicine, Section on Nephrology, Wake Forest School of Medicine, Winston-Salem, NC 27101, USA.

24. Channing Division of Network Medicine and Division of Pulmonary and Critical Care Medicine, Brigham and Women’s Hospital, Boston, MA 02115, USA.

25. National Heart, Lung, and Blood Institute’s, Boston University’s Framingham Heart Study, Framingham, MA 01701, USA.

26. National Heart, Lung and Blood Institute, Population Sciences Branch, Framingham, MA 01701, USA.

27. Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.

28. Department of Epidemiology, School of Public Health, University of Michigan, Ann Arbor, MI 48109, USA.

29. Department of Epidemiology, Tulane University School of Public Health and Tropical Medicine, New Orleans, LA 70112, USA.

30. Department of Epidemiology and Population Health, Albert Einstein College of Medicine, Bronx, NY 10461, USA.

31. Kaiser Permanente Washington Health Research Institute, Kaiser Permanente Washington, Seattle, WA 98101, USA.

32. Seattle Epidemiologic Research and Information Center, Department of Veterans Affairs Office of Research and Development, Seattle, WA 98108, USA.

33. Cardiovascular Health Research Unit, Department of Medicine, University of Washington, Seattle, WA 98101, USA.

34. Dean’s Office, College of Public Health, University of Kentucky, Lexington, KY 40506, USA.

35. University of Alabama at Birmingham, Birmingham, AL 35294, USA.

36. Department of Medicine, Jackson Heart Study, University of Mississippi Medical Center, Jackson, MS 39216, USA.

37. Department of Genetics, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.

38. Department of Medicine, University of Mississippi Medical Center, Jackson, MS 39216, USA.

39. Department of Health Sciences Research, Mayo Clinic, Rochester, MN 55905, USA.

40. Department of Public Health Sciences, Center for Public Health Genomics, University of Virginia, Charlottesville, VA 22903, USA.

41. Research Institute, Bloodworks Northwest, Seattle, WA 98102, USA.

42. Genome Science, University of Washington, Seattle, WA 98195, USA.

43. Vitalant Research Institute, San Francisco, CA 94105, USA.

44. Department of Human Genetics, University of Texas Rio Grande Valley School of Medicine, Brownsville, TX 78520, USA.

45. South Texas Diabetes and Obesity Institute, University of Texas Rio Grande Valley School of Medicine, Brownsville, TX 78520, USA.

46. Center for Individualized and Genomic Medicine Research (CIGMA), Henry Ford Health System, Detroit, MI 48202, USA.

47. Department of Medicine, Henry Ford Health System, Detroit, MI 48202, USA.

48. Division of Genetics, Genomics, and Precision Medicine, University of Arizona, Tucson, AZ 85721, USA.

49. Department of Medicine, University of Arizona, Tucson, AZ 85721, USA.

50. Wake Forest University School of Medicine, Winston-Salem, NC 27101, USA.

51. Department of Epidemiology and International Health Institute, Brown University School of Public Health, Providence, RI 02903, USA.

52. Division of Biostatistics, Washington University School of Medicine, Campus Box 8067, 660 S. Euclid Avenue, St. Louis, MO 63110, USA.

53. Department of Medical Research, Taichung Veterans General Hospital, 1650, Sec. 4, Taiwan Boulevard, Taichung City, Taiwan.

54. Division of Cardiology, Vanderbilt University Medical Center, Nashville, TN 37232, USA.

55. Division of Cardiology, University of Illinois at Chicago, Chicago, IL 60607, USA.

56. Departments of Medicine, Pharmacology, and Biomedical Informatics, Vanderbilt University Medical Center, Nashville, TN 37232, USA.

57. Department of Cardiology, Cedars-Sinai, Los Angeles, CA 90048, USA.

58. Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USA.

59. Division of Hematology and Oncology, Weill Cornell Medicine, New York, NY 10065, USA.

60. Englander Institute of Precision Medicine, Weill Cornell Medicine, New York 10065, NY, USA.

61. Regeneron Pharmaceuticals, Tarrytown, NY 10591, USA.

62. Cardiovascular Research Center, Massachusetts General Hospital, Boston, MA 02114, USA.

63. Department of Medicine, Harvard Medical School, Boston, MA 02115, USA.

64. Department of Pathology, Stanford University, Stanford, CA 94305, USA.

65. Division of Genetic Medicine, Department of Medicine, Vanderbilt University, Nashville, TN 37232, USA.

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.

Publisher

American Association for the Advancement of Science (AAAS)

Subject

Multidisciplinary

Link

https://www.science.org/doi/pdf/10.1126/sciadv.abm4945

Reference72 articles.

1. RNA sequence analysis reveals macroscopic somatic clonal expansion across normal tissues

2. Somatic mutations precede acute myeloid leukemia years before diagnosis

3. Prediction of acute myeloid leukaemia risk in healthy individuals

5. Clonal Hematopoiesis and Blood-Cancer Risk Inferred from Blood DNA Sequence

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