Brief Communication abstract


Nature Genetics 40, 1053 - 1055 (2008)
Published online: 30 July 2008 | doi:10.1038/ng.201

Identification of loci associated with schizophrenia by genome-wide association and follow-up

Michael C O'Donovan1, Nicholas Craddock1, Nadine Norton1, Hywel Williams1, Timothy Peirce1, Valentina Moskvina1, Ivan Nikolov1, Marian Hamshere1, Liam Carroll1, Lyudmila Georgieva1, Sarah Dwyer1, Peter Holmans1, Jonathan L Marchini2, Chris C A Spencer2, Bryan Howie2, Hin-Tak Leung3, Annette M Hartmann4, Hans-Jürgen Möller5, Derek W Morris6, YongYong Shi7, GuoYin Feng8, Per Hoffmann9, Peter Propping10, Catalina Vasilescu9, Wolfgang Maier11, Marcella Rietschel12, Stanley Zammit1, Johannes Schumacher13, Emma M Quinn6, Thomas G Schulze13, Nigel M Williams1, Ina Giegling4, Nakao Iwata14,15, Masashi Ikeda14,15, Ariel Darvasi16, Sagiv Shifman16, Lin He7,17, Jubao Duan18,19, Alan R Sanders18,19, Douglas F Levinson20, Pablo V Gejman18,19, Molecular Genetics of Schizophrenia Collaboration21, Sven Cichon9,10, Markus M Nöthen9,10, Michael Gill6, Aiden Corvin6, Dan Rujescu4, George Kirov1 & Michael J Owen1

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We carried out a genome-wide association study of schizophrenia (479 cases, 2,937 controls) and tested loci with P < 10-5 in up to 16,726 additional subjects. Of 12 loci followed up, 3 had strong independent support (P < 5 times 10-4), and the overall pattern of replication was unlikely to occur by chance (P = 9 times 10-8). Meta-analysis provided strongest evidence for association around ZNF804A (P = 1.61 times 10-7) and this strengthened when the affected phenotype included bipolar disorder (P = 9.96 times 10-9).

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  1. Department of Psychological Medicine, School of Medicine, Cardiff University, Cardiff, CF14 4XN, UK.
  2. Department of Statistics, University of Oxford, OX1 3TG, UK.
  3. Juvenile Diabetes Research Foundation/Wellcome Trust Diabetes and Inflammation Laboratory, Department of Medical Genetics, University of Cambridge, Cambridge, CB2 0XY, UK.
  4. Division of Molecular and Clinical Neurobiology, Ludwig-Maximilians-University, Nubetabaumstr. 7, 80336 Munich, Germany.
  5. Department of Psychiatry, Ludwig-Maximilians-University, Nubetabaumstr. 7, 80336 Munich, Germany.
  6. Neuropsychiatric Genetics Research Group, School of Medicine, Trinity College Dublin 8, Ireland.
  7. Bio-X Center, Shanghai Jiao Tong University, Shanghai 200030, China.
  8. Shanghai Institute of Mental Health, Shanghai 200030, China.
  9. Department of Genomics, Life and Brain Center, University of Bonn, Bonn 53105, Germany.
  10. Institute of Human Genetics, University of Bonn, Bonn 53105, Germany.
  11. Department of Psychiatry, University of Bonn, Bonn 53105, Germany.
  12. Central Institute for Mental Health, Division Genetic Epidemiology in Psychiatry, Mannheim 68159, Germany.
  13. Genetic Basis of Mood and Anxiety Disorders, US National Institute of Mental Health, National Institutes of Health, Bethesda, Maryland 20892, USA.
  14. Department of Psychiatry, Fujita Health University School of Medicine, Aichi 470-1192, Japan.
  15. Core Research for Evolutionary Science and Technology (CREST), Japan Science and Technology Agency, Saitama 332-0012, Japan.
  16. Department of Genetics, Institute of Life Sciences, Hebrew University of Jerusalem 91904, Israel.
  17. Institute for Nutritional Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China.
  18. Center for Psychiatric Genetics, Evanston Northwestern Healthcare (ENH), Evanston, Illinois 60201, USA.
  19. Feinberg School of Medicine, Northwestern University, Evanston, Illinois 60201, USA.
  20. Department of Psychiatry and Behavioral Sciences, Stanford University School of Medicine, California 94305, USA.
  21. A full list of authors and affiliations is provided at the end of this paper.
  22. School of Nursing, Louisiana State University Health Sciences Center, New Orleans, Louisiana 70112, USA.
  23. The Queensland Centre for Mental Health Research and The Queensland Institute for Medical Research, Wacol, Queensland 4076, Australia.
  24. Department of Psychiatry, University of Colorado Health Sciences Center, Denver, Colorado 80262, USA.
  25. Atlanta Veterans Affairs Medical Center and Department of Psychiatry and Behavioral Sciences, Emory University, Decatur, Georgia 30033, USA.
  26. Mental Health Clinical Research Center and Department of Psychiatry, University of Iowa College of Medicine, Iowa City, Iowa 52242, USA.
  27. Department of Psychiatry, Mount Sinai School of Medicine, New York, New York 10029, USA.
  28. Department of Psychiatry, University of California San Francisco, San Francisco, California 94121, USA.
  29. Departments of Psychiatry, Washington University, St. Louis, Missouri 63108, USA.
  30. Departments of Genetics, Washington University, St. Louis, Missouri 63108, USA.

Correspondence to: Michael C O'Donovan1 e-mail: wpcmod@cf.ac.uk

Correspondence to: Michael J Owen1 e-mail: wpcmjo@cf.ac.uk