title: The PDE4B gene confers sex-specific protection against schizophrenia.
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.
  
  
  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).
  
  
  CONCLUSIONS
  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.
authors.affiliation: Medical Genetics Section, School of Clinical and Molecular Medicine, Molecular Medicine Centre, University of Edinburgh, Royal Edinburgh Hospital, Edinburgh, UK. ben.pickard@ed.ac.uk
authors.forename: Benjamin S
authors.initials: BS
authors.lastname: Pickard
authors.forename: Philippa A
authors.initials: PA
authors.lastname: Thomson
authors.forename: Andrea
authors.initials: A
authors.lastname: Christoforou
authors.forename: Kathryn L
authors.initials: KL
authors.lastname: Evans
authors.forename: Stewart W
authors.initials: SW
authors.lastname: Morris
authors.forename: David J
authors.initials: DJ
authors.lastname: Porteous
authors.forename: Douglas H R
authors.initials: DH
authors.lastname: Blackwood
authors.forename: Walter J
authors.initials: WJ
authors.lastname: Muir
mesh_terms: D015105:3',5'-Cyclic-AMP Phosphodiesterases / Q000235:genetics*; D054703:Cyclic Nucleotide Phosphodiesterases, Type 4; D005260:Female; D005819:Genetic Markers; D005838:Genotype; D006801:Humans; D020641:Polymorphism, Single Nucleotide; D018570:Risk Assessment; D012559:Schizophrenia / Q000201:enzymology / Q000453:epidemiology / Q000235:genetics / Q000517:prevention & control*; D012606:Scotland / Q000453:epidemiology
chemical_list: D005819:Genetic Markers; D015105:3',5'-Cyclic-AMP Phosphodiesterases; D054703:Cyclic Nucleotide Phosphodiesterases, Type 4; C517360:PDE4B protein, human