1. Psychiatric and Neurodevelopmental Genetics Unit,
2. Center for Human Genetic Research, Massachusetts General Hospital, 185 Cambridge Street, Boston, Massachusetts 02114, USA.
3. Stanley Center for Psychiatric Research, The Broad Institute of Harvard and MIT, Cambridge, Massachusetts 02142, USA.
4. The Broad Institute of Harvard and MIT, Cambridge, Massachusetts 02142, USA.
5. Queensland Institute of Medical Research, 300 Herston Road, Brisbane, Queensland 4006, Australia.
6. MRC Centre for Neuropsychiatric Genetics and Genomics, Department of Psychological Medicine, School of Medicine, Cardiff University, Cardiff C14 4XN, UK.
7. Departments of Genetics, Psychiatry, and Epidemiology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599, USA.
8. Molecular Psychiatry Laboratory, Research Department of Mental Health Sciences, University College London Medical School, Windeyer Institute of Medical Sciences, 46 Cleveland Street, London W1T 4JF, UK.
9. Neuropsychiatric Genetics Research Group, Department of Psychiatry and Institute of Molecular Medicine, Trinity College Dublin, Dublin 2, Ireland.
10. Division of Psychiatry, University of Edinburgh, Royal Edinburgh Hospital, Edinburgh EH10 5HF, UK.
11. Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, SE-171 77 Stockholm, Sweden.
12. Department of Neuroscience, Psychiatry, Ulleråker, Uppsala University, SE-750 17 Uppsala, Sweden.
13. Center for Genomic Psychiatry, University of Southern California, Los Angeles, California 90033, USA.
14. Institute of Medical Sciences,
15. Department of Mental Health, University of Aberdeen, Aberdeen AB25 2ZD, UK.
16. Department of Medical Genetics, University Hospital Maichin Dom, Sofia 1431, Bulgaria.
17. Department of Psychiatry, First Psychiatric Clinic, Alexander University Hospital, Sofia 1431, Bulgaria.
18. West Berkshire NHS Trust, 25 Erleigh Road, Reading RG3 5LR, UK.
19. Department of Psychiatry, University of Oxford, Warneford Hospital, Headington, Oxford OX3 7JX, UK.
20. Ravenscraig Hospital, Inverkip Road, Greenock PA16 9HA, UK.
21. State University of New York – Upstate Medical University, Syracuse, New York 13210, USA.
22. Washington VA Medical Center, Washington DC 20422, USA.
23. Department of Psychiatry, Georgetown University School of Medicine, Washington DC 20057, USA.
24. Department of Psychiatry, Virginia Commonwealth University, Richmond, Virginia 23298, USA.
25. Department of Psychiatry, Sao Miguel, 9500-310 Azores, Portugal.
26. Department of Psychiatry University of Coimbra, 3004-504 Coimbra, Portugal.

Correspondence to: Correspondence and requests for materials should be addressed to P.S. (Email: sklar@chgr.mgh.harvard.edu) and S.M.P. (Email: shaun@pngu.mgh.harvard.edu).

Abstract

Schizophrenia is a severe mental disorder with a lifetime risk of about 1%, characterized by hallucinations, delusions and cognitive deficits, with heritability estimated at up to 80%^{1, 2}. We performed a genome-wide association study of 3,322 European individuals with schizophrenia and 3,587 controls. Here we show, using two analytic approaches, the extent to which common genetic variation underlies the risk of schizophrenia. First, we implicate the major histocompatibility complex. Second, we provide molecular genetic evidence for a substantial polygenic component to the risk of schizophrenia involving thousands of common alleles of very small effect. We show that this component also contributes to the risk of bipolar disorder, but not to several non-psychiatric diseases.

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