Preprint open access publication

Genome-wide association study identifies 30 Loci Associated with Bipolar Disorder

bioRxiv, Cold Spring Harbor Laboratory,

2017

DOI:10.1101/173062, Dimensions: pub.1091099884,

Authors

Stahl, Eli A * (1) (2)
Forstner, Andreas J (4) (5) (6)
Ripke, Stephan (2) (8) (9)
Mattheisen, Manuel (10) (11) (12) (13)
Wang, Yunpeng (14) (15)
Pers, Tune H (2) (19)
Agerbo, Esben (11) (12)
Akil, Huda (21)
Als, Thomas D (11) (12)
Casas, Miquel (35) (36) (37)
Curtis, David (7) (43)
Djurovic, Srdjan (48) (49)
Forty, Liz (20)
Frisén, Louise (52) (53)
Gade, Katrin (32) (54)
Grove, Jakob (11) (12)
Herms, Stefan (4) (5) (6)
Hoffmann, Per (4) (5) (6)
Jamain, Stéphane (64) (65)
Kennedy, James L (66) (67)
Kupka, Ralph (71) (72) (73)
Lee, Phil H (2) (8)
Li, Jun Z (21)
Mahon, Pamela B (47) (79)
McCarroll, Steve (2) (80)
Meng, Fan (21)
Morris, Derek W (83) (84)
Perlis, Roy H (8) (80)
Perry, Amy (57)
Purcell, Shaun M (1) (79)
Smeland, Olav B (45) (49) (97)
Strauss, John S (66) (67)
Weickert, Thomas W (59) (95)
Xi, Simon (103)
Xu, Wei (66) (104)
Agartz, Ingrid (13) (29) (105)
Alda, Martin (55) (106)
Bellivier, Frank (108) (109) (110) (111)
Børglum, Anders D (11) (12)
Daly, Mark J (2) (8)
Esko, Tõnu (2) (19) (80) (82)
Etain, Bruno (3) (109) (110) (111)
Frye, Mark (92)
Gershon, Elliot S (23) (114)
Hougaard, David M (11) (26)
Jones, Ian (20)
Kahn, René S (1) (30)
Landén, Mikael (13) (116)
Leboyer, Marion (65) (110) (111)
Martin, Nicholas G (18) (56)
Melle, Ingrid (49) (121)
Morken, Gunnar (122) (123)
Mors, Ole (11) (124)
Müller-Myhsok, Bertram (42) (125) (126)
Nordentoft, Merete (11) (128)
Oedegaard, Ketil J (48) (129)
Ribasés, M R Marta (35) (36) (37)
Rouleau, Guy A (130) (131)
Schofield, Peter R (59) (95)
Schulze, Thomas G (32) (47) (51) (54) (120)
Stefansson, Kari (17) (96)
Stordal, Eystein (123) (133)
Sullivan, Patrick F (13) (134)
Werge, Thomas (11) (128) (137)
Di Florio, Arianna (20) (134)
Cichon, Sven (4) (5) (6) (85)
Ophoff, Roel A (30) (31)
Andreassen, Ole A (49) (97)
Kelsoe, John * (45)

* Corresponding author

Affiliations

Organisations

  1. (1) Icahn School of Medicine at Mount Sinai, grid.59734.3c
  2. (2) Broad Institute, grid.66859.34
  3. (3) King's College London, grid.13097.3c
  4. (4) University of Bonn, grid.10388.32
  5. (5) University of Basel, grid.6612.3
  6. (6) University Hospital of Basel, grid.410567.1
  7. (7) University College London, grid.83440.3b
  8. (8) Massachusetts General Hospital, grid.32224.35
  9. (9) Charité, grid.6363.0
  10. (10) University Hospital Würzburg, grid.411760.5
  11. (11) Lundbeck Foundation, grid.452548.a
  12. (12) Aarhus University, grid.7048.b, AU
  13. (13) Karolinska Institute, grid.4714.6
  14. (14) Institute of Biological Psychiatry, Mental Health Centre Sct. Hans, Copenhagen, DK
  15. (15) University of Oslo, grid.5510.1
  16. (16) Amsterdam Neuroscience, grid.484519.5
  17. (17) CODE Genetics / Amgen, Reykjavik, IS
  18. (18) University of Queensland, grid.1003.2
  19. (19) Boston Children's Hospital, grid.2515.3
  20. (20) Cardiff University, grid.5600.3
  21. (21) University of Michigan, grid.214458.e
  22. (22) Mario Negri Institute for Pharmacological Research, grid.4527.4
  23. (23) Department of Psychiatry and Behavioral Neuroscience, University of Chicago, Chicago, IL, US
  24. (24) Berkshire Healthcare NHS Foundation Trust, grid.439510.a
  25. (25) Rush University Medical Center, grid.240684.c
  26. (26) State Serum Institute, grid.6203.7
  27. (27) Cornell University, grid.5386.8
  28. (28) Department of Psychiatry and Psychotherapy, University Hospital Carl Gustav Carus, Technische Universität Dresden, Dresden, DE
  29. (29) Diakonhjemmet Hospital, grid.413684.c
  30. (30) University Medical Center Utrecht, grid.7692.a
  31. (31) University of California, Los Angeles, grid.19006.3e
  32. (32) Institute of Psychiatric Phenomics and Genomics (IPPG), University Hospital, LMU Munich, Munich, DE
  33. (33) University of California, Irvine, grid.266093.8
  34. (34) University of California, San Francisco, grid.266102.1
  35. (35) Autonomous University of Barcelona, grid.7080.f
  36. (36) Hospital Universitari Vall d'Hebron, grid.411083.f
  37. (37) Institute of Health Carlos III, grid.413448.e
  38. (38) McGill University Health Centre, grid.63984.30
  39. (39) University of Edinburgh, grid.4305.2
  40. (40) University of Iowa Hospitals and Clinics, grid.412584.e
  41. (41) University of Southern California, grid.42505.36
  42. (42) Max Planck Institute of Psychiatry, grid.419548.5
  43. (43) Queen Mary University of London, grid.4868.2
  44. (44) Poznan University of Medical Sciences, grid.22254.33
  45. (45) University of California, San Diego, grid.266100.3
  46. (46) University of Antwerp, grid.5284.b
  47. (47) Johns Hopkins University, grid.21107.35
  48. (48) University of Bergen, grid.7914.b
  49. (49) Oslo University Hospital, grid.55325.34
  50. (50) Indiana University – Purdue University Indianapolis, grid.257413.6
  51. (51) Central Institute of Mental Health, grid.413757.3
  52. (52) Child and Adolescent Psychiatry Research Center, Stockholm, SE
  53. (53) Karolinska University Hospital, grid.24381.3c
  54. (54) University Medical Center Göttingen, grid.411984.1
  55. (55) Dalhousie University, grid.55602.34
  56. (56) QIMR Berghofer Medical Research Institute, grid.1049.c
  57. (57) University of Worcester, grid.189530.6
  58. (58) Peninsula College of Medicine and Dentistry, grid.467855.d
  59. (59) UNSW Sydney, grid.1005.4
  60. (60) University of Minnesota System, grid.437349.e
  61. (61) Instituto de Investigación Biomédica de Málaga, grid.452525.1
  62. (62) University of Tübingen, grid.10392.39
  63. (63) Howard University Hospital, grid.411399.7
  64. (64) Mondor Institute of Biomedical Research, grid.462410.5
  65. (65) Paris 12 Val de Marne University, grid.410511.0
  66. (66) University of Toronto, grid.17063.33
  67. (67) Centre for Addiction and Mental Health, grid.155956.b
  68. (68) University Hospital Frankfurt, grid.411088.4
  69. (69) University of Cincinnati, grid.24827.3b
  70. (70) Center for Research in Environmental Epidemiology, grid.417617.2
  71. (71) GGZ inGeest, grid.420193.d
  72. (72) VU University Medical Center, grid.16872.3a
  73. (73) Altrecht GGZ, grid.413664.2
  74. (74) North East London NHS Foundation Trust, grid.451079.e
  75. (75) University Hospital Cologne, grid.411097.a
  76. (76) HudsonAlpha Institute for Biotechnology, grid.417691.c
  77. (77) University of Illinois at Chicago, grid.185648.6
  78. (78) National Health Service Scotland, grid.422655.2
  79. (79) Brigham and Women's Hospital, grid.62560.37
  80. (80) Harvard University, grid.38142.3c
  81. (81) International Agency For Research On Cancer, grid.17703.32
  82. (82) University of Tartu, grid.10939.32
  83. (83) National University of Ireland, Galway, grid.6142.1
  84. (84) Trinity College Dublin, grid.8217.c
  85. (85) Forschungszentrum Jülich, grid.8385.6
  86. (86) VA San Diego Healthcare System, grid.410371.0
  87. (87) Umeå University, grid.12650.30
  88. (88) Clinical Center University of Sarajevo, grid.411735.5
  89. (89) Washington University in St. Louis, grid.4367.6
  90. (90) University of Granada, grid.4489.1
  91. (91) Vanderbilt University Medical Center, grid.412807.8
  92. (92) Mayo Clinic, grid.66875.3a
  93. (93) Stanford University, grid.168010.e
  94. (94) Scripps Health, grid.419722.b
  95. (95) Neuroscience Research Australia, grid.250407.4
  96. (96) University of Iceland, grid.14013.37
  97. (97) NORMENT, University of Oslo, Oslo, NO
  98. (98) PsyQ, grid.491389.e
  99. (99) University of Aberdeen, grid.7107.1
  100. (100) Federal Institute for Drugs and Medical Devices, grid.414802.b
  101. (101) Neurogenomics, TGen, Los Angeles, AZ, US
  102. (102) Psychiatry, Psychiatrisches Zentrum Nordbaden, Wiesloch, DE
  103. (103) Pfizer (United States), grid.410513.2
  104. (104) Princess Margaret Cancer Centre, grid.415224.4
  105. (105) NORMENT, KG Jebsen Centre for Psychosis Research, Division of Mental Health and Addiction, Institute of Clinical Medicine and Diakonhjemmet Hospital, University of Oslo, Oslo, NO
  106. (106) National Institute of Mental Health, grid.447902.c
  107. (107) University of Adelaide, grid.1010.0
  108. (108) Paris Bipolar and TRD Expert Centres, FondaMental Foundation, Paris, FR
  109. (109) Paris Diderot University, grid.7452.4
  110. (110) Assistance Publique -Hopitaux De Paris, grid.50550.35
  111. (111) French Institute of Health and Medical Research, grid.7429.8
  112. (112) University of Pennsylvania, grid.25879.31
  113. (113) University of Münster, grid.5949.1
  114. (114) University of Chicago, grid.170205.1
  115. (115) Spitalul Clinic de Psihiatrie Alexandru Obregia, grid.440274.1
  116. (116) University of Gothenburg, grid.8761.8
  117. (117) Janssen (United States), grid.497530.c
  118. (118) Maria Skłodowska-Curie Memorial Cancer Center and Institute of Oncology, grid.418165.f
  119. (119) Lindner Center of HOPE, grid.490303.d
  120. (120) National Institute of Mental Health, grid.416868.5
  121. (121) Division of Mental Health and Addiction, University of Oslo, Institute of Clinical Medicine, Oslo, NO
  122. (122) St Olav's University Hospital, grid.52522.32
  123. (123) Norwegian University of Science and Technology, grid.5947.f
  124. (124) Aarhus University Hospital, grid.154185.c, Central Denmark Region
  125. (125) Munich Cluster for Systems Neurology, grid.452617.3
  126. (126) University of Liverpool, grid.10025.36
  127. (127) University of Pittsburgh, grid.21925.3d
  128. (128) University of Copenhagen, grid.5254.6, KU
  129. (129) Haukeland University Hospital, grid.412008.f
  130. (130) Montreal Neurological Institute and Hospital, grid.416102.0
  131. (131) McGill University, grid.14709.3b
  132. (132) University of Bologna, grid.6292.f
  133. (133) Department of Psychiatry, Hospital Namsos, Namsos, NO
  134. (134) University of North Carolina at Chapel Hill, grid.10698.36
  135. (135) Dept of Psychiatry, Sankt Olavs Hospital Universitetssykehuset i Trondheim, Trondheim, NO
  136. (136) Clinical Institute of Neuroscience, Hospital Clinic, University of Barcelona, IDIBAPS, CIBERSAM, Barcelona, ES
  137. (137) Institute of Biological Psychiatry, MHC Sct. Hans, Mental Health Services Copenhagen, Roskilde, DK

Description

ABSTRACT Bipolar disorder is a highly heritable psychiatric disorder that features episodes of mania and depression. We performed the largest genome-wide association study to date, including 20,352 cases and 31,358 controls of European descent, with follow-up analysis of 822 sentinel variants at loci with P<1×10 -4 in an independent sample of 9,412 cases and 137,760 controls. In the combined analysis, 30 loci reached genome-wide significant evidence for association, of which 20 were novel. These significant loci contain genes encoding ion channels and neurotransmitter transporters ( CACNA1C , GRIN2A , SCN2A , SLC4A1 ), synaptic components ( RIMS1 , ANK3 ), immune and energy metabolism components. Bipolar disorder type I (depressive and manic episodes; ~ 73% of our cases) is strongly genetically correlated with schizophrenia whereas bipolar disorder type II (depressive and hypomanic episodes; ~ 17% of our cases) is more strongly correlated with major depressive disorder. These findings address key clinical questions and provide potential new biological mechanisms for bipolar disorder.

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Times Cited: 83

Field Citation Ratio (FCR): 22.52

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Green, Published