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PNAS 100 (15): 8993-8998

Copyright © 2003 by the National Academy of Sciences.

BIOLOGICAL SCIENCES / NEUROSCIENCE

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

David J. Gerber*, Diana Hall{dagger}, Tsuyoshi Miyakawa*, Sandra Demars{dagger}, Joseph A. Gogos{ddagger}, Maria Karayiorgou{dagger},§,¶, and Susumu Tonegawa*,§,¶

*Howard Hughes Medical Institute, RIKEN/Massachusetts Institute of Technology Neuroscience Research Center, The Picower Center for Learning and Memory, Departments of Biology and Brain and Cognitive Sciences, Massachusetts Institute of Technology, Cambridge, MA 02139; {dagger}Human Neurogenetics Laboratory, The Rockefeller University, New York, NY 10021; and {ddagger}Department of Physiology and Cellular Biophysics, Center for Neurobiology and Behavior, Columbia University College of Physicians and Surgeons, New York, NY 10032

Contributed by Susumu Tonegawa, May 15, 2003

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.

To whom correspondence may be addressed. E-mail: karayim{at}rockefeller.edu or tonegawa{at}mit.edu.

§ M.K. and S.T. contributed equally to this work.

Abbreviation: SNP, single-nucleotide polymorphism.

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