Common polygenic variation contributes to risk of schizophrenia and bipolar disorder

David M St Clair, Margaret Purcell, Naomi R Wray, Jeffery Stone, Peter M Visscher, Michael C O'Donovan, Patrick F Sullivan, Pamela Sklar, The International Schizophrenia Consortium (ISC)

Research output: Contribution to journalLetterpeer-review

3685 Citations (Scopus)


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%. 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.
Original languageEnglish
Pages (from-to)748-752
Number of pages5
Issue number7256
Early online date1 Jul 2009
Publication statusPublished - 6 Aug 2009


  • alleles
  • bipolar disorder
  • case-control studies
  • Europe
  • female
  • gene frequency
  • genetic predisposition to disease
  • genetic variation
  • genome, human
  • genome-wide association study
  • humans
  • major histocompatibility complex
  • male
  • models, genetic
  • multifactorial inheritance
  • polymorphism, single nucleotide
  • schizophrenia


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