The PDE4B gene confers sex-specific protection against schizophrenia

B. S. Pickard, P. A. Thomson, A. Christoforou, K. L. Evans, S. W. Morris, D. J. Porteous, D. H. Blackwood, W. J. Muir

Research output: Contribution to journalArticle

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Abstract

BACKGROUND: Phosphodiesterase 4B (PDE4B) is a candidate gene for schizophrenia and affective disorders through its disruption by a chromosomal translocation in an individual with schizophrenia, its inhibition by the antidepressant rolipram, and its physical interaction with another key candidate, Disrupted in Schizophrenia (DISC1). OBJECTIVE: To determine the contribution made by PDE4B to the population risk of schizophrenia and bipolar disorder by carrying out a case-control association study. METHODS: Twenty-six tagging single nucleotide polymorphisms were selected across the PDE4B gene and genotyped in DNA samples from 386 schizophrenia cases, 368 bipolar disorder cases and 455 controls. MAIN RESULTS: Single single nucleotide polymorphisms and a resulting haplotype conferred a protective effect against schizophrenia in the female population. The haplotype result remained significant after correction for multiple testing (P=0.012). CONCLUSION: The observation that a PDE4B haplotype alters the genetic risk of schizophrenia in the Scottish population complements the known participation of this gene in biological processes associated with mental illness. Further studies are needed to replicate this finding and identify underlying sequence variants.
LanguageEnglish
Pages129-133
Number of pages5
JournalPsychiatric Genetics
Volume17
DOIs
Publication statusPublished - Jun 2007

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Type 4 Cyclic Nucleotide Phosphodiesterase
Schizophrenia
Genes
Haplotypes
Bipolar Disorder
Single Nucleotide Polymorphism
Rolipram
Population
Biological Phenomena
Genetic Translocation
Mood Disorders
Antidepressive Agents
Case-Control Studies
DNA

Keywords

  • epidemiology
  • PDE4B gene
  • schizophrenia
  • genetic markers

Cite this

Pickard, B. S., Thomson, P. A., Christoforou, A., Evans, K. L., Morris, S. W., Porteous, D. J., ... Muir, W. J. (2007). The PDE4B gene confers sex-specific protection against schizophrenia. Psychiatric Genetics, 17, 129-133. https://doi.org/10.1097/YPG.0b013e328014492b
Pickard, B. S. ; Thomson, P. A. ; Christoforou, A. ; Evans, K. L. ; Morris, S. W. ; Porteous, D. J. ; Blackwood, D. H. ; Muir, W. J. / The PDE4B gene confers sex-specific protection against schizophrenia. In: Psychiatric Genetics. 2007 ; Vol. 17. pp. 129-133.
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Pickard, BS, Thomson, PA, Christoforou, A, Evans, KL, Morris, SW, Porteous, DJ, Blackwood, DH & Muir, WJ 2007, 'The PDE4B gene confers sex-specific protection against schizophrenia' Psychiatric Genetics, vol. 17, pp. 129-133. https://doi.org/10.1097/YPG.0b013e328014492b

The PDE4B gene confers sex-specific protection against schizophrenia. / Pickard, B. S.; Thomson, P. A.; Christoforou, A.; Evans, K. L.; Morris, S. W.; Porteous, D. J.; Blackwood, D. H.; Muir, W. J.

In: Psychiatric Genetics, Vol. 17, 06.2007, p. 129-133.

Research output: Contribution to journalArticle

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AU - Pickard, B. S.

AU - Thomson, P. A.

AU - Christoforou, A.

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AU - Blackwood, D. H.

AU - Muir, W. J.

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N2 - BACKGROUND: Phosphodiesterase 4B (PDE4B) is a candidate gene for schizophrenia and affective disorders through its disruption by a chromosomal translocation in an individual with schizophrenia, its inhibition by the antidepressant rolipram, and its physical interaction with another key candidate, Disrupted in Schizophrenia (DISC1). OBJECTIVE: To determine the contribution made by PDE4B to the population risk of schizophrenia and bipolar disorder by carrying out a case-control association study. METHODS: Twenty-six tagging single nucleotide polymorphisms were selected across the PDE4B gene and genotyped in DNA samples from 386 schizophrenia cases, 368 bipolar disorder cases and 455 controls. MAIN RESULTS: Single single nucleotide polymorphisms and a resulting haplotype conferred a protective effect against schizophrenia in the female population. The haplotype result remained significant after correction for multiple testing (P=0.012). CONCLUSION: The observation that a PDE4B haplotype alters the genetic risk of schizophrenia in the Scottish population complements the known participation of this gene in biological processes associated with mental illness. Further studies are needed to replicate this finding and identify underlying sequence variants.

AB - BACKGROUND: Phosphodiesterase 4B (PDE4B) is a candidate gene for schizophrenia and affective disorders through its disruption by a chromosomal translocation in an individual with schizophrenia, its inhibition by the antidepressant rolipram, and its physical interaction with another key candidate, Disrupted in Schizophrenia (DISC1). OBJECTIVE: To determine the contribution made by PDE4B to the population risk of schizophrenia and bipolar disorder by carrying out a case-control association study. METHODS: Twenty-six tagging single nucleotide polymorphisms were selected across the PDE4B gene and genotyped in DNA samples from 386 schizophrenia cases, 368 bipolar disorder cases and 455 controls. MAIN RESULTS: Single single nucleotide polymorphisms and a resulting haplotype conferred a protective effect against schizophrenia in the female population. The haplotype result remained significant after correction for multiple testing (P=0.012). CONCLUSION: The observation that a PDE4B haplotype alters the genetic risk of schizophrenia in the Scottish population complements the known participation of this gene in biological processes associated with mental illness. Further studies are needed to replicate this finding and identify underlying sequence variants.

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Pickard BS, Thomson PA, Christoforou A, Evans KL, Morris SW, Porteous DJ et al. The PDE4B gene confers sex-specific protection against schizophrenia. Psychiatric Genetics. 2007 Jun;17:129-133. https://doi.org/10.1097/YPG.0b013e328014492b