The PDE4B gene confers sex-specific protection against schizophrenia

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.