Variation at the DAOA/G30 locus influences susceptibility to major mood episodes but not psychosis in schizophrenia and bipolar disorder

Nigel M. Williams, Elaine K. Green, Stuart Macgregor, Sarah Dwyer, Nadine Norton, Hywel Williams, Rachel Raybould, Detelina Grozeva, Marian Hamshere, Stanley Zammit, Lisa Jones, Alastair Cardno, George Kirov, Ian Jones, Michael C. O'Donovan, Michael J. Owen, Nick Craddock

Research output: Contribution to journalArticle

116 Citations (Scopus)

Abstract

Context: Variation at the DAOA/G30 locus has been described to be associated with both schizophrenia and bipolar disorder, but there is little consistency between studies of the tested polymorphisms or variants showing association. Objectives: To obtain a stringent replication of association in large samples of both disorders using consistent clinical and laboratory methods, and to test the hypothesis that association at DAOA/G30 identifies an underlying domain of psychopathological abnormalities that cuts across traditional diagnostic categories. Design: A systematic study of polymorphisms at DAOA/ G30 using genetic case-control association analysis. Setting: Subjects were unrelated and ascertained from general psychiatric inpatient and outpatient services. Participants: White persons from the United Kingdom meeting criteria for DSM-IV schizophrenia (n=709) or bipolar I disorder (n=706) and 1416 ethnically matched controls. Methods: Nine polymorphisms that tag common genetic variations at DAOA/G30 were genotyped in all of the individuals, and comparisons were made between affected and unaffected individuals. Results: We identified significant association (P=.01-.047) between 3 single-nucleotide polymorphisms and bipolar disorder but failed to find association with schizophrenia. Analyses across the traditional diagnostic categories revealed significant evidence (P=.002-.02) for association with 4 single-nucleotide polymorphisms in the subset of cases (n=818) in which episodes of major mood disorder had occurred (gene-wide P=.009). We found a similar pattern of association in bipolar cases and in schizophrenia cases in which individuals had experienced major mood disorder. In contrast, we found no evidence for association in the subset of cases (n=1153) in which psychotic features occurred (all P>.08). Conclusions: Despite being originally described as a schizophrenia susceptibility locus, our data suggest that variation at the DAOA/G30 locus does not primarily increase susceptibility for prototypical schizophrenia or psychosis. Instead, our results imply that variation at the DAOA/G30 locus influences susceptibility to episodes of mood disorder across the traditional bipolar and schizophrenia categories.

Original languageEnglish (US)
Pages (from-to)366-373
Number of pages8
JournalArchives of General Psychiatry
Volume63
Issue number4
DOIs
StatePublished - Apr 2006
Externally publishedYes

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Bipolar Disorder
Psychotic Disorders
Schizophrenia
Mood Disorders
Single Nucleotide Polymorphism
Ambulatory Care
Locus
Psychosis
Mood
Susceptibility
Diagnostic and Statistical Manual of Mental Disorders
Psychiatry
Inpatients
Polymorphism
Genes

ASJC Scopus subject areas

  • Arts and Humanities (miscellaneous)
  • Psychiatry and Mental health

Cite this

Variation at the DAOA/G30 locus influences susceptibility to major mood episodes but not psychosis in schizophrenia and bipolar disorder. / Williams, Nigel M.; Green, Elaine K.; Macgregor, Stuart; Dwyer, Sarah; Norton, Nadine; Williams, Hywel; Raybould, Rachel; Grozeva, Detelina; Hamshere, Marian; Zammit, Stanley; Jones, Lisa; Cardno, Alastair; Kirov, George; Jones, Ian; O'Donovan, Michael C.; Owen, Michael J.; Craddock, Nick.

In: Archives of General Psychiatry, Vol. 63, No. 4, 04.2006, p. 366-373.

Research output: Contribution to journalArticle

Williams, NM, Green, EK, Macgregor, S, Dwyer, S, Norton, N, Williams, H, Raybould, R, Grozeva, D, Hamshere, M, Zammit, S, Jones, L, Cardno, A, Kirov, G, Jones, I, O'Donovan, MC, Owen, MJ & Craddock, N 2006, 'Variation at the DAOA/G30 locus influences susceptibility to major mood episodes but not psychosis in schizophrenia and bipolar disorder', Archives of General Psychiatry, vol. 63, no. 4, pp. 366-373. https://doi.org/10.1001/archpsyc.63.4.366
Williams, Nigel M. ; Green, Elaine K. ; Macgregor, Stuart ; Dwyer, Sarah ; Norton, Nadine ; Williams, Hywel ; Raybould, Rachel ; Grozeva, Detelina ; Hamshere, Marian ; Zammit, Stanley ; Jones, Lisa ; Cardno, Alastair ; Kirov, George ; Jones, Ian ; O'Donovan, Michael C. ; Owen, Michael J. ; Craddock, Nick. / Variation at the DAOA/G30 locus influences susceptibility to major mood episodes but not psychosis in schizophrenia and bipolar disorder. In: Archives of General Psychiatry. 2006 ; Vol. 63, No. 4. pp. 366-373.
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abstract = "Context: Variation at the DAOA/G30 locus has been described to be associated with both schizophrenia and bipolar disorder, but there is little consistency between studies of the tested polymorphisms or variants showing association. Objectives: To obtain a stringent replication of association in large samples of both disorders using consistent clinical and laboratory methods, and to test the hypothesis that association at DAOA/G30 identifies an underlying domain of psychopathological abnormalities that cuts across traditional diagnostic categories. Design: A systematic study of polymorphisms at DAOA/ G30 using genetic case-control association analysis. Setting: Subjects were unrelated and ascertained from general psychiatric inpatient and outpatient services. Participants: White persons from the United Kingdom meeting criteria for DSM-IV schizophrenia (n=709) or bipolar I disorder (n=706) and 1416 ethnically matched controls. Methods: Nine polymorphisms that tag common genetic variations at DAOA/G30 were genotyped in all of the individuals, and comparisons were made between affected and unaffected individuals. Results: We identified significant association (P=.01-.047) between 3 single-nucleotide polymorphisms and bipolar disorder but failed to find association with schizophrenia. Analyses across the traditional diagnostic categories revealed significant evidence (P=.002-.02) for association with 4 single-nucleotide polymorphisms in the subset of cases (n=818) in which episodes of major mood disorder had occurred (gene-wide P=.009). We found a similar pattern of association in bipolar cases and in schizophrenia cases in which individuals had experienced major mood disorder. In contrast, we found no evidence for association in the subset of cases (n=1153) in which psychotic features occurred (all P>.08). Conclusions: Despite being originally described as a schizophrenia susceptibility locus, our data suggest that variation at the DAOA/G30 locus does not primarily increase susceptibility for prototypical schizophrenia or psychosis. Instead, our results imply that variation at the DAOA/G30 locus influences susceptibility to episodes of mood disorder across the traditional bipolar and schizophrenia categories.",
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AU - Williams, Nigel M.

AU - Green, Elaine K.

AU - Macgregor, Stuart

AU - Dwyer, Sarah

AU - Norton, Nadine

AU - Williams, Hywel

AU - Raybould, Rachel

AU - Grozeva, Detelina

AU - Hamshere, Marian

AU - Zammit, Stanley

AU - Jones, Lisa

AU - Cardno, Alastair

AU - Kirov, George

AU - Jones, Ian

AU - O'Donovan, Michael C.

AU - Owen, Michael J.

AU - Craddock, Nick

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N2 - Context: Variation at the DAOA/G30 locus has been described to be associated with both schizophrenia and bipolar disorder, but there is little consistency between studies of the tested polymorphisms or variants showing association. Objectives: To obtain a stringent replication of association in large samples of both disorders using consistent clinical and laboratory methods, and to test the hypothesis that association at DAOA/G30 identifies an underlying domain of psychopathological abnormalities that cuts across traditional diagnostic categories. Design: A systematic study of polymorphisms at DAOA/ G30 using genetic case-control association analysis. Setting: Subjects were unrelated and ascertained from general psychiatric inpatient and outpatient services. Participants: White persons from the United Kingdom meeting criteria for DSM-IV schizophrenia (n=709) or bipolar I disorder (n=706) and 1416 ethnically matched controls. Methods: Nine polymorphisms that tag common genetic variations at DAOA/G30 were genotyped in all of the individuals, and comparisons were made between affected and unaffected individuals. Results: We identified significant association (P=.01-.047) between 3 single-nucleotide polymorphisms and bipolar disorder but failed to find association with schizophrenia. Analyses across the traditional diagnostic categories revealed significant evidence (P=.002-.02) for association with 4 single-nucleotide polymorphisms in the subset of cases (n=818) in which episodes of major mood disorder had occurred (gene-wide P=.009). We found a similar pattern of association in bipolar cases and in schizophrenia cases in which individuals had experienced major mood disorder. In contrast, we found no evidence for association in the subset of cases (n=1153) in which psychotic features occurred (all P>.08). Conclusions: Despite being originally described as a schizophrenia susceptibility locus, our data suggest that variation at the DAOA/G30 locus does not primarily increase susceptibility for prototypical schizophrenia or psychosis. Instead, our results imply that variation at the DAOA/G30 locus influences susceptibility to episodes of mood disorder across the traditional bipolar and schizophrenia categories.

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