☆ 4.7 Article

Genetic influences on schizophrenia and subcortical brain volumes: large-scale proof of concept

NATURE NEUROSCIENCE (2016)

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Journal

NATURE NEUROSCIENCE
Volume 19, Issue 3, Pages 420-+

Publisher

NATURE PUBLISHING GROUP
DOI: 10.1038/nn.4228

Keywords

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Categories

Neurosciences

Funding

  1. US National Institute of Mental Health (NIMH) [U01 MH094421]
  2. Netherlands Scientific Organization [NWO 480-05-003]
  3. Max Planck Society
  4. Max-Planck-Forderstiftung
  5. DFG Center for Nanoscale Microscopy AMP
  6. Molecular Physiology of the Brain (CNMPB), Gottingen, Germany
  7. NIMH [P50 MH080272, U01 MH081928, R01 MH092380, K99 MH101367, MH085548, MH085542, MH071681, MH061884, MH58693, MH52618, R01 MH083094, R01 MH041953, R01 MH068881]
  8. Massachusetts General Hospital Executive Committee on Research
  9. NCRR [RR026075]
  10. Department of Veterans Affairs Merit Review Program
  11. Lundbeck Foundation
  12. Danish Strategic Research Council
  13. Aarhus University
  14. Stanley Research Foundation
  15. UK Medical Research Council (MRC) Centre [G0800509]
  16. MRC Programme [G0801418]
  17. European Community's Seventh Framework Programme [HEALTH-F2-2010-241909]
  18. European Union Seventh Framework Programme (FP7) [279227]
  19. MRC/Welsh Assembly Government
  20. Margaret Temple Award from the British Medical Association
  21. Wellcome Trust [076113/C/04/Z, 076113/CI04/Z, 072894/Z/03/Z, 090532/Z/09/Z, 075491/Z/04/B, 068545/Z/02]
  22. National Institute for Health Research programme grant [RP-PG-0310-1002]
  23. WTCCC2 grant [WTCCC-084710]
  24. Janssen Research Foundation, Beerse, Belgium
  25. Netherlands Organization for Health Research and Development (ZonMw) in the Mental Health program
  26. Danish Council for Strategic Research [09-067048]
  27. Danish National Advanced Technology Foundation [001-2009-2]
  28. Lundbeck Foundation [R24-A3243]
  29. EU
  30. Wellcome Trust as part of the WTCCC2 project
  31. MRC
  32. Research Council of Norway [213837, 217776, 223273]
  33. South-East Norway Health Authority [2013-123]
  34. K. G. Jebsen Foundation
  35. Donald and Barbara Zucker Foundation
  36. North Shore - Long Island Jewish Health System Foundation
  37. Stanley Foundation
  38. NARSAD
  39. SynSys [EU FP7-242167]
  40. Sigrid Juselius Foundation
  41. Academy of Finland [251704]
  42. Sohlberg Foundation
  43. Swedish Research Council [2006-4472, 2009-5269, 2009-3413, 345-2003-3883, 315-2004-6977, 80576801, 70374401]
  44. County Council of Vasterbotten, Sweden
  45. County Council of Norrbotten, Sweden
  46. Bank of Sweden Tercentenary Foundation
  47. Swedish Council for Planning and Coordination of Research
  48. Swedish Council for Research in the Humanities and Social Sciences
  49. Swedish Council for Social Research
  50. Estonian Ministry of Science and Education [SF0180142s08]
  51. US National Institutes of Health (NIH) [R01 DK075787]
  52. University of Tartu [SP1GVARENG]
  53. European Regional Development Fund [3.2.0304.11-0312]
  54. FP7 grant [313010]
  55. Singapore National Medical Research Council [NMRC/TCR/003/2008]
  56. Singapore Biomedical Research Council
  57. Singapore Agency for Science, Technology and Research (A*STAR)
  58. Uppsala University, Uppsala University Hospital, Science for Life Laboratory
  59. Stockholm County Council
  60. Karolinska Insititutet
  61. Australian Schizophrenia Research Bank
  62. National Health and Medical Research Council [386500]
  63. Pratt Foundation
  64. Ramsay Health Care
  65. Viertel Charitable Foundation
  66. Schizophrenia Research Institute
  67. NSW Department of Health
  68. National Health and Medical Research Council (Australia)
  69. Australian National Health and Medical Research Council
  70. German Federal Ministry of Education and Research (BMBF) through the Integrated Genome Research Network MooDS under the National Genome Research Network plus (NGFNplus) [01GS08144, 01GS08147]
  71. Integrated Network IntegraMent (Integrated Understanding of Causes and Mechanisms in Mental Disorders), under e:Med Programme (GlaxoSmithKline)
  72. Bavarian Ministry of Commerce
  73. BMBF [01GS0481]
  74. German Research Foundation (DFG)
  75. Alfried Krupp von Bohlen und Halbach-Stiftung
  76. European Union [279227, HEALTH-F4-2009-242257, HEALTH-2011-1.1-2]
  77. Stanley Medical Research Institute
  78. Stanley Center for Psychiatric Research
  79. Sylvan Herman Foundation
  80. Friedman Brain Institute at the Mount Sinai School of Medicine
  81. Karolinska Institutet, Karolinska University Hospital
  82. Swedish County Council
  83. Soderstrom Konigska Foundation
  84. Juvenile Diabetes Research Foundation [WT0618S8]
  85. National Institute of Health Research of England
  86. Walter E. Nichols, M. D., Professorship in the School of Medicine
  87. Eleanor Nichols Endowment
  88. Walter F. AMP
  89. Rachael L. Nichols Endowment
  90. William and Mary McIvor Endowment, Stanford University
  91. NIH [MH67257, MH59588, MH59571, MH59565, MH59587, MH60870, MH59566, MH59586, MH61675, MH60879, MH81800, MH46276, MH46289, MH46318, MH79469, MH79470, R01D0042157-01A, MH081802]
  92. Genetic Association Information Network (GAIN)
  93. Paul Michael Donovan Charitable Foundation
  94. National Center for Research Resources [U54 RR020278]
  95. WTCCC2 project [085475/B/08/Z, 085475/Z/08/Z]
  96. MRC [G0000934]
  97. Hong Kong Research Grants Council project [GRF 774707M, 777511M, 776412M, 776513M]
  98. NIH institutes contributing to the Big Data to Knowledge (BD2K) initiative [U54 EB020403]
  99. NIBIB
  100. NCI.ADNI
  101. Alzheimer's Disease Neuroimaging Initiative (ADNI) (NIH) [U01 AG024904]
  102. US Department of Defense [W81XWH-12-2-0012]
  103. US National Institute on Aging
  104. National Institute of Biomedical Imaging and Bioengineering
  105. Canadian Institutes of Health Research
  106. Northern California Institute for Research and Education
  107. Knut and Alice Wallenberg Foundation
  108. Torsten and Ragnar Soderbergs Foundation
  109. HelseVest RHF [911554]
  110. Scottish Mental Health Research Network
  111. National Alliance for Research on Schizophrenia and Depression (NARSAD) Independent Investigator Award
  112. Health Foundation Clinician Scientist Fellowship
  113. Biobanking and Biomolecular Resources Research Infrastructure (Netherlands) (BBMRI-NL)
  114. Hersenstichting Nederland
  115. Netherlands Organization for Scientific Research (NWO)
  116. European Community [602450, 602805]
  117. Vici grant from the NWO [016.130.669]
  118. Center for Brain Science Neuroinformatics Research Group
  119. Athinoula A. Martinos Center for Biomedical Imaging
  120. Center for Human Genetic Research
  121. European Union-funded FP6 Integrated Project IMAGEN [LSHM-CT-2007-037286]
  122. FP7 projects [602450, 603016]
  123. Innovative Medicine Initiative Project EU-AIMS [115300-2]
  124. Medical Research Council programme grant [93558]
  125. NIHR Biomedical Research Center
  126. Swedish Research Council (FORMAS)
  127. BMBF (eMED SysAlc) [01ZX1311A, 1EV0711]
  128. BMBF through the Integrated Genome Research Network MooDS under the National Genome Research Network plus (NGFNplus) [01GS08144, 01GS08147, 01GS08148]
  129. Integrated Network IntegraMent, under the auspices of the e:Med Programme [01ZX1314A, 01ZX1314C, 01ZX1314G]
  130. Exzellenz-Stiftung of the Max Planck Society
  131. BMBF in the framework of the National Genome Research Network (NGFN) [FKZ 01GS0481]
  132. Bergen Research Foundation
  133. University of Bergen
  134. Dr Einar Martens Fund
  135. K. G. Jebsen Foundation and the Research Council of Norway
  136. Netherlands Organization for Scientific Research (Geestkracht program grant) [10-000-1002]
  137. Center for Medical Systems Biology (CSMB, NWO Genomics)
  138. Biobanking and Biomolecular Resources Research Infrastructure (BBMRI-NL)
  139. VU University's Institutes for Health and Care Research (EMGO+)
  140. Neuroscience Campus Amsterdam
  141. University Medical Center Groningen, Leiden University Medical Center
  142. Genetic Association Information Network (GAIN) of the Foundation for the National Institutes of Health
  143. NWO
  144. NWO large investment grant [1750102007010]
  145. Radboud University Nijmegen Medical Center
  146. University Medical Center Groningen and Accare
  147. VU University Amsterdam
  148. European Community's Seventh Framework Programme (FP7) [602450, 602805, 278948]
  149. NWO [MW904-61-193, MaGW-nr 400-07-080, MagW 480-04-004, 51.02.060, 668.772, NWO/SPI 56-464-14192]
  150. European Research Council [ERC-230374]
  151. Utrecht University
  152. NWO Brain and Cognition [433-09-220]
  153. Australian National Health and Medical Research Council (NHMRC)/Australian Research Council Strategic Award [401162]
  154. NHMRC [1045325, 310667, 401184, 525453, 568940, 389875, 486682, 1009064]
  155. Commonwealth Scientific and Industrial Research Organisation Flagship Collaboration Fund grant
  156. Australian Government
  157. Alzheimer's Australia Dementia Research Foundation
  158. National Science Foundation [BCS-1229450]
  159. Autism Speaks
  160. Australian Research Council [FT110100548, FT0991634]
  161. NHMRC fellowship [619667]
  162. BMBF (grants) [01ZZ9603, 01ZZ0103, 01ZZ0403]
  163. DFG [GR 1912/5-1]
  164. German Ministry of Cultural Affairs
  165. Social Ministry of the Federal State of Mecklenburg-West Pomerania
  166. Siemens Healthcare, Erlangen, Germany
  167. Federal State of Mecklenburg-West Pomerania
  168. University Medicine Greifswald
  169. NHMRC program [401184, 350833, 568969]
  170. NHMRC project grant [525453]
  171. NHMRC capacity building grant [568940]
  172. The NIMH [R01 MH078075, MH065580, MH001760, RC2 MH089964, R01 MH084098, K01 MH085812, R01 MH100141, R01 MH077139, R01 MH095034, R01 MH062276, R01 MH068922, R01 MH068921, MH 41953, MH083094, K99MH102357]
  173. [CZ. 2.16/3.1.00/24022OPPK]
  174. [NT/13770-4]
  175. [00064203 FN Motol]
  176. [1RC2 MH089951]
  177. [1RC2 MH089995]
  178. [R01MH62873]
  179. [R01 NS080655]
  180. [R01AG040060]
  181. [R01 EB008432]
  182. [R01 MH097268]
  183. [R01 MH085667]
  184. [R01 MH089722]
  185. [ERC-2010-AdG 268800-NEUROSCHEMA]
  186. Australian Research Council [FT110100548, FT0991634] Funding Source: Australian Research Council
  187. Lundbeck Foundation [R155-2014-1724] Funding Source: researchfish
  188. Medical Research Council [G1100616, MR/L010305/1, MR/K026992/1, MR/L016400/1, G0000934, G0901858, G0800509, G0801418, MC_UU_12013/2, MC_UU_12013/1, MR/P005748/1, MR/L023784/2] Funding Source: researchfish
  189. Wellcome Trust [100309/A/12/Z] Funding Source: researchfish
  190. MRC [MR/L023784/2, MR/P005748/1, G0800509, G1100616, G0801418, MC_UU_12013/2, MR/L016400/1, G0000934, G0901858, MC_UU_12013/1] Funding Source: UKRI

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Schizophrenia is a devastating psychiatric illness with high heritability. Brain structure and function differ, on average, between people with schizophrenia and healthy individuals. As common genetic associations are emerging for both schizophrenia and brain imaging phenotypes, we can now use genome-wide data to investigate genetic overlap. Here we integrated results from common variant studies of schizophrenia (33,636 cases, 43,008 controls) and volumes of several (mainly subcortical) brain structures (11,840 subjects). We did not find evidence of genetic overlap between schizophrenia risk and subcortical volume measures either at the level of common variant genetic architecture or for single genetic markers. These results provide a proof of concept (albeit based on a limited set of structural brain measures) and define a roadmap for future studies investigating the genetic covariance between structural or functional brain phenotypes and risk for psychiatric disorders.

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