The NeuroBioBank Whole-Genome Catalog: Sequencing from human brain donors with central nervous system disorders

  1. Daniel Hupalo
  2. Jacob L. McCauley
  3. Lissette Gomez
  4. Anthony J. Griswold
  5. Gabriela Hoher
  6. Ioanna Konidari
  7. Jose Lorenzo
  8. Griffin S. Parker
  9. Julianna Pascual
  10. Amanda R. Sandford
  11. Patrice L. Whitehead
  12. David A. Davis
  13. Susanna Garamszegi
  14. S. Humayun Gultekin
  15. Xiaoyan Sun
  16. Regina T. Vontell
  17. Michael Chatigny
  18. Darren Chernicky
  19. Myrtha M. Constant
  20. Isabelle G. Darling
  21. David J. Ennulat
  22. John M. Esposito
  23. Kiely Morris
  24. Elisabeth S. Lawton
  25. Neda R. Morakabati
  26. Phyllis Oduor
  27. Allison P. Rodgers
  28. Lorelle A. Sang
  29. Kathleen M. Sullivan
  30. Catalina J. Tabit
  31. Tori Turpin
  32. Aya Zeabi
  33. Tina Zheng
  34. Sabina Berretta
  35. Torsten Klengel
  36. Derek H. Oakley
  37. W. Brad Ruzicka
  38. Thomas Blanchard
  39. Eric Ho
  40. Robert Johnson
  41. Alexandra LeFevre
  42. Maxwell Bustamante
  43. Vahram Haroutunian
  44. Pavel Katsel
  45. Christine Marino
  46. Stephen Panopoulos
  47. Dushyant P. Purohit
  48. Michael Wysocki
  49. Jill R. Glausier
  50. David .A. Lewis
  51. Rashed M. Nagra
  52. Camille Alba
  53. Julianna Martin
  54. Elizabeth Rice
  55. John Rosenberger
  56. Grace Smith
  57. Gauthaman Sukumar
  58. Miranda Tompkins
  59. Matthew Wilkerson
  60. Clifton L. Dalgard
  61. William K. Scott
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Abstract

Central nervous system diseases are a prevailing cause of morbidity and mortality worldwide, and are influenced by environmental and biological factors including genetic risk. Here we generated genome-wide genetic data on a large cohort of brain tissue donors with in-depth clinical and neuropathological phenotyping, allowing for broad investigations into the risk and mechanisms of these neurological, neurodevelopmental, and psychiatric conditions. This resource consists of 9,663 donors with array-based genotyping and 9,543 donors with whole-genome sequencing completed. The clinical diagnoses of these donors include 148 central nervous system diseases clustered in 15 broad categories by ICD-10 coding. These donors were collected by six repositories comprising the NIH NeuroBioBank, with an average participant age of 60 years. While primarily older individuals of European descent, the cohort also contains younger donors and individuals from non-European backgrounds. Variants detected by Whole-Genome Sequencing (WGS) were called genome-wide and annotated to describe their functional impact, resulting in 171,121,209 unique mutations and 1,078,774 non-silent mutations. This whole-genome resource has been made available in the NIMH Data Archive (<ext-link xmlns:xlink="http://www.w3.org/1999/xlink" ext-link-type="uri" xlink:href="http://nda.nih.gov">nda.nih.gov</ext-link>) and accompanying deep demographic and phenotypic descriptions are available at the NeuroBioBank Portal (<ext-link xmlns:xlink="http://www.w3.org/1999/xlink" ext-link-type="uri" xlink:href="http://neurobiobank.nih.gov">neurobiobank.nih.gov</ext-link>). To illustrate an application of this resource, we replicated the strong association observed in previous studies between pathogenic CAG repeat expansions in theHTTgene with the clinical diagnosis of Huntington’s disease.

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