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 journalLetter

2699 Citations (Scopus)

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%. 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
JournalNature
Volume460
Issue number7256
Early online date1 Jul 2009
DOIs
Publication statusPublished - 6 Aug 2009

Fingerprint

Bipolar Disorder
Schizophrenia
Delusions
Genome-Wide Association Study
Hallucinations
Major Histocompatibility Complex
Mental Disorders
Molecular Biology
Alleles

Keywords

  • 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

Cite this

St Clair, D. M., Purcell, M., Wray, N. R., Stone, J., Visscher, P. M., O'Donovan, M. C., ... The International Schizophrenia Consortium (ISC) (2009). Common polygenic variation contributes to risk of schizophrenia and bipolar disorder. Nature, 460(7256), 748-752. https://doi.org/10.1038/nature08185

Common polygenic variation contributes to risk of schizophrenia and bipolar disorder. / St Clair, David M; Purcell, Margaret; Wray, Naomi R; Stone, Jeffery; Visscher, Peter M; O'Donovan, Michael C; Sullivan, Patrick F; Sklar, Pamela; The International Schizophrenia Consortium (ISC).

In: Nature, Vol. 460, No. 7256, 06.08.2009, p. 748-752.

Research output: Contribution to journalLetter

St Clair, DM, Purcell, M, Wray, NR, Stone, J, Visscher, PM, O'Donovan, MC, Sullivan, PF, Sklar, P & The International Schizophrenia Consortium (ISC) 2009, 'Common polygenic variation contributes to risk of schizophrenia and bipolar disorder', Nature, vol. 460, no. 7256, pp. 748-752. https://doi.org/10.1038/nature08185
St Clair DM, Purcell M, Wray NR, Stone J, Visscher PM, O'Donovan MC et al. Common polygenic variation contributes to risk of schizophrenia and bipolar disorder. Nature. 2009 Aug 6;460(7256):748-752. https://doi.org/10.1038/nature08185
St Clair, David M ; Purcell, Margaret ; Wray, Naomi R ; Stone, Jeffery ; Visscher, Peter M ; O'Donovan, Michael C ; Sullivan, Patrick F ; Sklar, Pamela ; The International Schizophrenia Consortium (ISC). / Common polygenic variation contributes to risk of schizophrenia and bipolar disorder. In: Nature. 2009 ; Vol. 460, No. 7256. pp. 748-752.
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