☆ 4.8 Article

Meta-analysis of genome-wide association studies discovers multiple loci for chronic lymphocytic leukemia

NATURE COMMUNICATIONS (2016)

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NATURE COMMUNICATIONS
Volume 7, Issue -, Pages -

Publisher

NATURE PUBLISHING GROUP
DOI: 10.1038/ncomms10933

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Categories

Multidisciplinary Sciences

Funding

  1. intramural programme of the Division of Cancer Epidemiology and Genetics
  2. National Cancer Institute [30 CA086862, P30 CA15083, P30 CA015083]
  3. US National Institutes of Health
  4. Intramural Research Program of the NIH
  5. Department of Health and Human Services [N01-CN-45165, N01-RC-45035, N01-RC-37004, HHSN261201000006C]
  6. Canadian Institutes for Health Research (CIHR)
  7. Michael Smith Foundation for Health Research
  8. American Cancer Society
  9. NCI
  10. Division of Cancer Epidemiology and Genetics
  11. Centers for Disease Control and Prevention National Program of Cancer Registries
  12. National Cancer Institute Surveillance Epidemiology and End Results program
  13. Leukaemia AMP
  14. Lymphoma Research
  15. Association pour la Recherche contre le Cancer (ARC)
  16. Institut National du Cancer (INCa)
  17. Fondation de France
  18. Fondation contre la Leucemie
  19. Agence nationale de securite sanitaire de l'alimentation, de l'environnement et du travail (ANSES)
  20. Coordinated Action [006438, SP23-CT-2005-006438]
  21. HuGeF (Human Genetics Foundation), Torino, Italy
  22. European Commission [QLK4-CT-2000-00422, FOOD-CT-2006-023103]
  23. Spanish Ministry of Health [CIBERESP, PI11/01810, PI14/01219, RCESP C03/09, RTICESP C03/10, RTIC RD06/0020/0095]
  24. Marato de TV3 Foundation [051210]
  25. Agencia de Gestiod' AjutsUniversitarisi de Recerca-Generalitat de Catalunya [2014SRG756]
  26. NIH [NO1-CO-12400, CA118444, CA148690, CA92153, K08CA134919, CA167552, CA149445, CA098122, CA098566, K07 CA115687, R01 CA92153, CA186107, CA87969, CA49449, 5R01 CA69669-02, CA1046282, CA154643, HHSN261201000026C]
  27. Compagnia di San Paolo-Programma Oncologia
  28. Federal Office for Radiation Protection [StSch4261, StSch4420]
  29. Jose Carreras Leukemia Foundation [DJCLS-R12/23]
  30. German Federal Ministry for Education and Research [BMBF-01-EO-1303]
  31. Health Research Board, Ireland
  32. MH CZ-DRO (MMCI) [00209805]
  33. RECAMO [CZ.1.05/2.1.00/03.0101]
  34. Fondation de France and Association de Recherche Contre le Cancer
  35. National Cancer Institute and Veterans Affairs Research Service
  36. Leukemia AMP
  37. Lymphoma Society Career Development Award
  38. Bernstein Family Fund for Leukemia and Lymphoma Research
  39. National Center for Advancing Translational Science [UL1 TR000135]
  40. NCI Specialized Programs of Research Excellence (SPORE) in Human Cancer [P50 CA97274]
  41. Henry J. Predolin Foundation
  42. Italian Association for Cancer Research (AIRC) [11855]
  43. Fondazione Banco di Sardegna
  44. Regione Autonoma della Sardegna (LR7) [CRP-59812/2012]
  45. VicHealth and Cancer Council Victoria
  46. Australian NHMRC [209057, 251553, 504711]
  47. infrastructure provided by Cancer Council Victoria
  48. Instituto de Salud Carlos III (ISCIII-Spanish Government) [CIBERESP, PI11/01810, PI14/01219, RCESP C03/09]
  49. Agencia de Gestiod' AjutsUniversitarisi de Recerca (AGAUR)-Generalitat de Catalunya (Catalonian Government) [2014SGR756]
  50. Center for Translational and Public Health Genomics
  51. MSKCC-Geoffrey Beene Cancer Research Grant, Lymphoma Foundation [LF5541]
  52. Barbara K. Lipman Lymphoma Research Fund [74419]
  53. Robert and Kate Niehaus Clinical Cancer Genetics Research Initiative [57470]
  54. ENCODE
  55. NCI-SEER-Intramural Research Program of the National Cancer Institute
  56. Public Health Service [N01-PC-65064, N01-PC-67008, N01-PC-67009, N01-PC-67010, N02-PC-71105]
  57. Australian National Health and Medical Research Council [ID990920]
  58. Cancer Council NSW
  59. University of Sydney Faculty of Medicine
  60. NYU-WHS-National Cancer Institute [R01 CA098661, P30 CA016087]
  61. National Institute of Environmental Health Sciences [ES000260]
  62. Intramural Research Program of the National Cancer Institute
  63. Division of Cancer Prevention
  64. DHHS
  65. SCALE-Swedish Cancer Society [2009/659]
  66. Stockholm County Council [20110209]
  67. Strategic Research Program in Epidemiology at Karolinska Institute
  68. Swedish Cancer Society grant [02 6661]
  69. California Department of Health Services, statewide cancer reporting program mandated by California Health and Safety Code Section [103885]
  70. National Cancer Institute's Surveillance, Epidemiology, and End Results Program [HHSN261201000140C]
  71. Cancer Prevention Institute of California [HHSN261201000035C]
  72. University of Southern California [HHSN261201000034C]
  73. Public Health Institute
  74. Centers for Disease Control and Prevention's National Program of Cancer Registries [1U58 DP000807-01]
  75. UTAH/Sheffield-NIH [CA134674]
  76. Utah Population Database (UPDB)
  77. Utah Cancer Registry (UCR)
  78. Huntsman Cancer Institute (HCI)
  79. HCI Cancer Center Support grant [P30 CA42014]
  80. National Cancer Institute SEER Program
  81. Utah State Department of Health
  82. University of Utah
  83. Yorkshire Cancer Research
  84. US Department of Health and Human Services [HHSN268201100046C, HHSN268201100001C, HHSN268201100002C, HHSN268201100003C, HHSN268201100004C, HHSN271201100004C]
  85. YALE-National Cancer Institute [CA62006, CA165923]
  86. NSFC-the National Natural Science Foundation of China [61471078]
  87. National Heart, Lung, and Blood Institute
  88. Canadian Cancer Society
  89. Cancer Research UK
  90. Cancer Research Ireland, Czech Republic
  91. Sheffield Experimental Cancer Medicine Centre
  92. Cancer Research UK [16491] Funding Source: researchfish

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Chronic lymphocytic leukemia (CLL) is a common lymphoid malignancy with strong heritability. To further understand the genetic susceptibility for CLL and identify common loci associated with risk, we conducted a meta-analysis of four genome-wide association studies (GWAS) composed of 3,100 cases and 7,667 controls with follow-up replication in 1,958 cases and 5,530 controls. Here we report three new loci at 3p24.1 (rs9880772, EOMES, P = 2.55 x 10(-11)), 6p25.2 (rs73718779, SERPINB6, P = 1.97 x 10(-8)) and 3q28 (rs9815073, LPP, P = 3.62 x 10(-8)), as well as a new independent SNP at the known 2q13 locus (rs9308731, BCL2L11, P = 1.00 x 10(-11)) in the combined analysis. We find suggestive evidence (P<5 x 10(-7)) for two additional new loci at 4q24 (rs10028805, BANK1, P = 7.19 x 10(-8)) and 3p22.2 (rs1274963, CSRNP1, P = 2.12 x 10(-7)). Pathway analyses of new and known CLL loci consistently show a strong role for apoptosis, providing further evidence for the importance of this biological pathway in CLL susceptibility.

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