Evidence for association of schizophrenia with genetic variation in the 8p21.3 gene, PPP3CC, encoding the calcineurin gamma subunit

Proc Natl Acad Sci U S A. 2003 Jul 22;100(15):8993-8. doi: 10.1073/pnas.1432927100. Epub 2003 Jul 8.

Abstract

Schizophrenia is a severe psychiatric disorder characterized by a complex mode of inheritance. Forebrain-specific CNB knockout mice display a spectrum of behavioral abnormalities related to altered behaviors observed in schizophrenia patients. To examine whether calcineurin dysfunction is involved in schizophrenia etiology, we undertook studies of an initial subset of calcineurin-related genes, prioritizing ones that map to loci previously implicated in schizophrenia by linkage studies. Transmission disequilibrium studies in a large sample of affected families detected association of the PPP3CC gene, which encodes the calcineurin gamma catalytic subunit, with disease. Our results identify PPP3CC, located at 8p21.3, as a potential schizophrenia susceptibility gene and support the proposal that alterations in calcineurin signaling contribute to schizophrenia pathogenesis.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adult
  • Base Sequence
  • Calcineurin / chemistry
  • Calcineurin / genetics*
  • Calcineurin / physiology
  • Chromosome Mapping
  • Chromosomes, Human, Pair 8 / genetics
  • DNA, Complementary / genetics
  • Genetic Variation*
  • Haplotypes
  • Humans
  • Polymorphism, Genetic
  • Protein Subunits
  • Schizophrenia / etiology
  • Schizophrenia / genetics*
  • Signal Transduction

Substances

  • DNA, Complementary
  • Protein Subunits
  • Calcineurin