Article open access publication

Atlas of prostate cancer heritability in European and African-American men pinpoints tissue-specific regulation

Nature Communications, Springer Nature, ISSN 2041-1723

Volume 7, 1, 2016

DOI:10.1038/ncomms10979, Dimensions: pub.1029725277, PMC: PMC4829663, PMID: 27052111,

Authors

Gusev, Alexander * (1) (2)
Li, Fugen (4)
Zheng, Wei (11)
Yeboah, Edward D. (12) (13)
Tettey, Yao (12) (13)
Adjei, Andrew A. (12) (13)
Tay, Evelyn (12) (13)
John, Esther M (16) (17)
Hsing, Ann W. (16) (17)
Chu, Lisa (16) (17)
Blot, William J. (11) (19)
Eeles, Rosalind A. (27) (28)
Muir, Kenneth (30) (31)
Giles, Graham G (32) (33)
Aly, Markus (34) (35)
Key, Tim J. (40) (41)
Travis, Ruth C. (40) (41)
Neal, David E. (29) (42)
Hamdy, Freddie C. (44) (45)
Pashayan, Nora (29) (46)
Stanford, Janet L (22) (47)
Teerlink, Craig (53) (54)
Johansson, Mattias (69) (70)
Navarro, Carmen (72) (73)
Trichopoulos, Dimitrios (2) (75) (76)
Vineis, Paolo (74) (77)
Trynka, Gosia (2) (78)
Raychaudhuri, Soumya (1) (2) (31)
Price, Alkes L. (1) (2)

* Corresponding author

Affiliations

Organisations

  1. (1) Broad Institute, grid.66859.34
  2. (2) Harvard University, grid.38142.3c
  3. (3) University of California, Los Angeles, grid.19006.3e
  4. (4) Dana-Farber Cancer Institute, grid.65499.37
  5. (5) University of Southern California, grid.42505.36
  6. (6) University of Arizona, grid.134563.6
  7. (7) The University of Texas MD Anderson Cancer Center, grid.240145.6
  8. (8) Henry Ford Hospital, grid.413103.4
  9. (9) Stony Brook University, grid.36425.36
  10. (10) Johns Hopkins University, grid.21107.35
  11. (11) Vanderbilt University, grid.152326.1
  12. (12) Korle Bu Teaching Hospital, grid.415489.5
  13. (13) University of Ghana, grid.8652.9
  14. (14) Westat (United States), grid.280561.8
  15. (15) University of California, Berkeley, grid.47840.3f
  16. (16) Cancer Prevention Institute of California, grid.280669.3
  17. (17) Stanford University, grid.168010.e
  18. (18) Northwestern University, grid.16753.36
  19. (19) International Epidemiology Institute, grid.419344.f
  20. (20) Translational Genomics Research Institute, grid.250942.8
  21. (21) University of the West Indies, grid.412886.1
  22. (22) Fred Hutchinson Cancer Research Center, grid.270240.3
  23. (23) Cleveland Clinic, grid.239578.2
  24. (24) University of California, San Francisco, grid.266102.1
  25. (25) Makerere University, grid.11194.3c
  26. (26) National Cancer Institute, grid.48336.3a
  27. (27) Royal Marsden National Health Service (NHS) Foundation Trust, London and Sutton, UK
  28. (28) Institute of Cancer Research, grid.18886.3f
  29. (29) University of Cambridge, grid.5335.0
  30. (30) University of Warwick, grid.7372.1
  31. (31) University of Manchester, grid.5379.8
  32. (32) University of Melbourne, grid.1008.9
  33. (33) Cancer Council Victoria, grid.3263.4
  34. (34) Karolinska Institute, grid.4714.6
  35. (35) Department of Clinical Sciences at Danderyds Hospital, 171 77, Stockholm, Sweden
  36. (36) University of Turku, grid.1374.1
  37. (37) Tampere University, grid.502801.e
  38. (38) Faculty of Health and Medical Sciences, University of Copenhagen, 1165, Copenhagen, Densmark
  39. (39) Herlev Hospital, grid.411900.d, Capital Region
  40. (40) Nuffield Department of Population Health, Cancer Epidemiology
  41. (41) University of Oxford, grid.4991.5
  42. (42) Cancer Research UK Cambridge Institute, grid.470869.4
  43. (43) University of Bristol, grid.5337.2
  44. (44) Aarhus University, grid.7048.b, AU
  45. (45) Faculty of Medical Science, University of Oxford, John Radcliffe Hospital, OX1 3PN, Oxford, UK
  46. (46) University College London, grid.83440.3b
  47. (47) University of Washington, grid.34477.33
  48. (48) Mayo Clinic, grid.66875.3a
  49. (49) University Hospital Ulm, grid.410712.1
  50. (50) Rechts der Isar Hospital, grid.15474.33
  51. (51) Division of Urologic Surgery, Brigham and Womens Hospital, Dana-Farber Cancer Institute, 75 Francis Street, 02115, Boston, Massachusetts, USA
  52. (52) Pomeranian Medical University, grid.107950.a
  53. (53) George E. Wahlen Department of VA Medical Center, grid.413886.0
  54. (54) University of Utah, grid.223827.e
  55. (55) German Cancer Research Center, grid.7497.d
  56. (56) Moffitt Cancer Center, grid.468198.a
  57. (57) Department of Urology and Alexandrovska University Hospital, Medical University, 1431, Sofia, Bulgaria
  58. (58) Medical University of Sofia, grid.410563.5
  59. (59) Queensland University of Technology, grid.1024.7
  60. (60) QIMR Berghofer Medical Research Institute, grid.1049.c
  61. (61) University of Porto, grid.5808.5
  62. (62) Portuguese Oncology Institute, grid.418711.a
  63. (63) University of Surrey, grid.5475.3
  64. (64) National Institutes of Health, grid.94365.3d
  65. (65) Johns Hopkins Medicine, grid.469474.c
  66. (66) University of Colorado Denver, grid.241116.1
  67. (67) American Cancer Society, grid.422418.9
  68. (68) Brigham and Women's Hospital, grid.62560.37
  69. (69) International Agency For Research On Cancer, grid.17703.32
  70. (70) Umeå University, grid.12650.30
  71. (71) University of Hawaii at Manoa, grid.410445.0
  72. (72) Department of Epidemiology, Regional Health Authority, 30009, Murcia, Spain
  73. (73) Institute of Health Carlos III, grid.413448.e
  74. (74) Imperial College London, grid.7445.2
  75. (75) Academy of Athens, grid.417593.d
  76. (76) Hellenic Health Foundation, grid.424637.0
  77. (77) HuGeF Foundation, 10126, Torino, Italy
  78. (78) Wellcome Sanger Institute, grid.10306.34

Description

Although genome-wide association studies have identified over 100 risk loci that explain ∼33% of familial risk for prostate cancer (PrCa), their functional effects on risk remain largely unknown. Here we use genotype data from 59,089 men of European and African American ancestries combined with cell-type-specific epigenetic data to build a genomic atlas of single-nucleotide polymorphism (SNP) heritability in PrCa. We find significant differences in heritability between variants in prostate-relevant epigenetic marks defined in normal versus tumour tissue as well as between tissue and cell lines. The majority of SNP heritability lies in regions marked by H3k27 acetylation in prostate adenoc7arcinoma cell line (LNCaP) or by DNaseI hypersensitive sites in cancer cell lines. We find a high degree of similarity between European and African American ancestries suggesting a similar genetic architecture from common variation underlying PrCa risk. Our findings showcase the power of integrating functional annotation with genetic data to understand the genetic basis of PrCa.

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2016: Realized

Research area: Medicine

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2016: Level 2

Research area: Medicine

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Times Cited: 35

Field Citation Ratio (FCR): 7.27

Relative Citation ratio (RCR): 1.13

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