Evidence for association of schizophrenia with genetic variation in the 8p21.3 gene, PPP3CC, encoding the calcineurin gamma subunit.
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.
Gerber
David J
DJ
Howard Hughes Medical Institute, RIKEN/Massachusetts Institute of Technology Neuroscience Research Center, The Picower Center for Learning and Memory, Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
Hall
Diana
D
Miyakawa
Tsuyoshi
T
Demars
Sandra
S
Gogos
Joseph A
JA
Karayiorgou
Maria
M
Tonegawa
Susumu
S
D000328:Adult; D001483:Base Sequence; D019703:Calcineurin / Q000737:chemistry / Q000235:genetics* / Q000502:physiology; D002874:Chromosome Mapping; D002898:Chromosomes, Human, Pair 8 / Q000235:genetics; D018076:DNA, Complementary / Q000235:genetics; D014644:Genetic Variation; D006239:Haplotypes; D006801:Humans; D011110:Polymorphism, Genetic; D021122:Protein Subunits; D012559:Schizophrenia / Q000209:etiology / Q000235:genetics*; D015398:Signal Transduction
D018076:DNA, Complementary; D021122:Protein Subunits; D019703:Calcineurin