Neuregulin 1 and Susceptibility to Schizophrenia
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 bet...
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ftpubmed:oai:pubmedcentral.nih.gov:378543 2023-05-15T16:50:19+02:00 Neuregulin 1 and Susceptibility to Schizophrenia 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 2002-10 http://www.ncbi.nlm.nih.gov/pmc/articles/PMC378543 http://www.ncbi.nlm.nih.gov/pubmed/12145742 en eng The American Society of Human Genetics http://www.ncbi.nlm.nih.gov/pmc/articles/PMC378543 http://www.ncbi.nlm.nih.gov/pubmed/12145742 © 2002 by The American Society of Human Genetics. All rights reserved. Articles Text 2002 ftpubmed 2013-08-29T22:11:42Z 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. Text Iceland PubMed Central (PMC) |
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Articles 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 Neuregulin 1 and Susceptibility to Schizophrenia |
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description |
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. |
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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 |
author_facet |
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 |
author_sort |
Stefansson, Hreinn |
title |
Neuregulin 1 and Susceptibility to Schizophrenia |
title_short |
Neuregulin 1 and Susceptibility to Schizophrenia |
title_full |
Neuregulin 1 and Susceptibility to Schizophrenia |
title_fullStr |
Neuregulin 1 and Susceptibility to Schizophrenia |
title_full_unstemmed |
Neuregulin 1 and Susceptibility to Schizophrenia |
title_sort |
neuregulin 1 and susceptibility to schizophrenia |
publisher |
The American Society of Human Genetics |
publishDate |
2002 |
url |
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC378543 http://www.ncbi.nlm.nih.gov/pubmed/12145742 |
genre |
Iceland |
genre_facet |
Iceland |
op_relation |
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC378543 http://www.ncbi.nlm.nih.gov/pubmed/12145742 |
op_rights |
© 2002 by The American Society of Human Genetics. All rights reserved. |
_version_ |
1766040478855200768 |