2.50
Hdl Handle:
http://hdl.handle.net/2336/31233
Title:
Neuregulin 1 and susceptibility to schizophrenia
Authors:
Stefansson, Hreinn; Sigurdsson, Engilbert; Steinthorsdottir, Valgerdur; Bjornsdottir, Soley; Sigmundsson, Thordur; Ghosh, Shyamali; Brynjolfsson, Jon; Gunnarsdottir, Steinunn; Ivarsson, Omar; Chou, Thomas T; Hjaltason, Omar; Birgisdottir, Birgitta; Jonsson, Helgi; Gudnadottir, Vala G; Gudmundsdottir, Elsa; Bjornsson, Asgeir; Ingvarsson, Brynjolfur; Ingason, Andres; Sigfusson, Sigmundur; Hardardottir, Hronn; Harvey, Richard P; Lai, Donna; Zhou, Mingdong; Brunner, Daniela; Mutel, Vincent; Gonzalo, Acuna; Lemke, Greg; Sainz, Jesus; Johannesson, Gardar; Andresson, Thorkell; Gudbjartsson, Daniel; Manolescu, Andrei; Frigge, Michael L; Gurney, Mark E; Kong, Augustine; Gulcher, Jeffrey R; Petursson, Hannes; Stefansson, Kari
Citation:
Am. J. Hum. Genet. 2002, 71(4):877-92
Issue Date:
1-Oct-2002
Abstract:
The cause of schizophrenia is unknown, but it has a significant genetic component. Pharmacologic studies, studies of gene expression in man, and studies of mouse mutants suggest involvement of glutamate and dopamine neurotransmitter systems. However, so far, strong association has not been found between schizophrenia and variants of the genes encoding components of these systems. Here, we report the results of a genomewide scan of schizophrenia families in Iceland; these results support previous work, done in five populations, showing that schizophrenia maps to chromosome 8p. Extensive fine-mapping of the 8p locus and haplotype-association analysis, supplemented by a transmission/disequilibrium test, identifies neuregulin 1 (NRG1) as a candidate gene for schizophrenia. NRG1 is expressed at central nervous system synapses and has a clear role in the expression and activation of neurotransmitter receptors, including glutamate receptors. Mutant mice heterozygous for either NRG1 or its receptor, ErbB4, show a behavioral phenotype that overlaps with mouse models for schizophrenia. Furthermore, NRG1 hypomorphs have fewer functional NMDA receptors than wild-type mice. We also demonstrate that the behavioral phenotypes of the NRG1 hypomorphs are partially reversible with clozapine, an atypical antipsychotic drug used to treat schizophrenia.
Description:
To access full text version of this article. Please click on the hyperlink "View/Open" at the bottom of this page
Additional Links:
http://www.sciencedirect.com/science/article/B8JDD-4PYSFD6-J/1/d8488e3081ae23e30a31f6b1ec48865a

Full metadata record

DC FieldValue Language
dc.contributor.authorStefansson, Hreinn-
dc.contributor.authorSigurdsson, Engilbert-
dc.contributor.authorSteinthorsdottir, Valgerdur-
dc.contributor.authorBjornsdottir, Soley-
dc.contributor.authorSigmundsson, Thordur-
dc.contributor.authorGhosh, Shyamali-
dc.contributor.authorBrynjolfsson, Jon-
dc.contributor.authorGunnarsdottir, Steinunn-
dc.contributor.authorIvarsson, Omar-
dc.contributor.authorChou, Thomas T-
dc.contributor.authorHjaltason, Omar-
dc.contributor.authorBirgisdottir, Birgitta-
dc.contributor.authorJonsson, Helgi-
dc.contributor.authorGudnadottir, Vala G-
dc.contributor.authorGudmundsdottir, Elsa-
dc.contributor.authorBjornsson, Asgeir-
dc.contributor.authorIngvarsson, Brynjolfur-
dc.contributor.authorIngason, Andres-
dc.contributor.authorSigfusson, Sigmundur-
dc.contributor.authorHardardottir, Hronn-
dc.contributor.authorHarvey, Richard P-
dc.contributor.authorLai, Donna-
dc.contributor.authorZhou, Mingdong-
dc.contributor.authorBrunner, Daniela-
dc.contributor.authorMutel, Vincent-
dc.contributor.authorGonzalo, Acuna-
dc.contributor.authorLemke, Greg-
dc.contributor.authorSainz, Jesus-
dc.contributor.authorJohannesson, Gardar-
dc.contributor.authorAndresson, Thorkell-
dc.contributor.authorGudbjartsson, Daniel-
dc.contributor.authorManolescu, Andrei-
dc.contributor.authorFrigge, Michael L-
dc.contributor.authorGurney, Mark E-
dc.contributor.authorKong, Augustine-
dc.contributor.authorGulcher, Jeffrey R-
dc.contributor.authorPetursson, Hannes-
dc.contributor.authorStefansson, Kari-
dc.date.accessioned2008-07-08T09:28:10Z-
dc.date.available2008-07-08T09:28:10Z-
dc.date.issued2002-10-01-
dc.date.submitted2008-07-08-
dc.identifier.citationAm. J. Hum. Genet. 2002, 71(4):877-92en
dc.identifier.issn0002-9297-
dc.identifier.pmid12145742-
dc.identifier.doi10.1086/342734-
dc.identifier.urihttp://hdl.handle.net/2336/31233-
dc.descriptionTo access full text version of this article. Please click on the hyperlink "View/Open" at the bottom of this pageen
dc.description.abstractThe cause of schizophrenia is unknown, but it has a significant genetic component. Pharmacologic studies, studies of gene expression in man, and studies of mouse mutants suggest involvement of glutamate and dopamine neurotransmitter systems. However, so far, strong association has not been found between schizophrenia and variants of the genes encoding components of these systems. Here, we report the results of a genomewide scan of schizophrenia families in Iceland; these results support previous work, done in five populations, showing that schizophrenia maps to chromosome 8p. Extensive fine-mapping of the 8p locus and haplotype-association analysis, supplemented by a transmission/disequilibrium test, identifies neuregulin 1 (NRG1) as a candidate gene for schizophrenia. NRG1 is expressed at central nervous system synapses and has a clear role in the expression and activation of neurotransmitter receptors, including glutamate receptors. Mutant mice heterozygous for either NRG1 or its receptor, ErbB4, show a behavioral phenotype that overlaps with mouse models for schizophrenia. Furthermore, NRG1 hypomorphs have fewer functional NMDA receptors than wild-type mice. We also demonstrate that the behavioral phenotypes of the NRG1 hypomorphs are partially reversible with clozapine, an atypical antipsychotic drug used to treat schizophrenia.en
dc.language.isoenen
dc.publisherUniversity of Chicago Pressen
dc.relation.urlhttp://www.sciencedirect.com/science/article/B8JDD-4PYSFD6-J/1/d8488e3081ae23e30a31f6b1ec48865aen
dc.subject.meshAnimalsen
dc.subject.meshChromosome Mappingen
dc.subject.meshChromosomes, Human, Pair 8en
dc.subject.meshDisease Models, Animalen
dc.subject.meshFemaleen
dc.subject.meshGenetic Predisposition to Diseaseen
dc.subject.meshHaplotypesen
dc.subject.meshHumansen
dc.subject.meshMaleen
dc.subject.meshMiceen
dc.subject.meshMice, Inbred C57BLen
dc.subject.meshMolecular Sequence Dataen
dc.subject.meshNeuregulin-1en
dc.subject.meshReceptor, Epidermal Growth Factoren
dc.subject.meshSchizophreniaen
dc.titleNeuregulin 1 and susceptibility to schizophreniaen
dc.typeArticleen
dc.contributor.departmentdeCODE Genetics, Reykjavik, Iceland. kstefans@decode.is.en
dc.identifier.journalAmerican journal of human geneticsen

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