Neuregulin 1 and susceptibility to schizophrenia
To access full text version of this article. Please click on the hyperlink "View/Open" at the bottom of this page 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 sugges...
Published in: | The American Journal of Human Genetics |
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University of Chicago Press
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Online Access: | http://hdl.handle.net/2336/31233 https://doi.org/10.1086/342734 |
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ftlandspitaliuni:oai:www.hirsla.lsh.is:2336/31233 2023-05-15T16:51:12+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 deCODE Genetics, Reykjavik, Iceland. kstefans@decode.is. 2008-07-08 http://hdl.handle.net/2336/31233 https://doi.org/10.1086/342734 en eng University of Chicago Press http://www.sciencedirect.com/science/article/B8JDD-4PYSFD6-J/1/d8488e3081ae23e30a31f6b1ec48865a Am. J. Hum. Genet. 2002, 71(4):877-92 0002-9297 12145742 doi:10.1086/342734 http://hdl.handle.net/2336/31233 American journal of human genetics Animals Chromosome Mapping Chromosomes Human Pair 8 Disease Models Animal Female Genetic Predisposition to Disease Haplotypes Humans Male Mice Inbred C57BL Molecular Sequence Data Neuregulin-1 Receptor Epidermal Growth Factor Schizophrenia Article 2008 ftlandspitaliuni https://doi.org/10.1086/342734 2022-05-29T08:21:10Z To access full text version of this article. Please click on the hyperlink "View/Open" at the bottom of this page 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. Article in Journal/Newspaper Iceland Hirsla - Landspítali University Hospital research archive The American Journal of Human Genetics 71 4 877 892 |
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Hirsla - Landspítali University Hospital research archive |
op_collection_id |
ftlandspitaliuni |
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English |
topic |
Animals Chromosome Mapping Chromosomes Human Pair 8 Disease Models Animal Female Genetic Predisposition to Disease Haplotypes Humans Male Mice Inbred C57BL Molecular Sequence Data Neuregulin-1 Receptor Epidermal Growth Factor Schizophrenia |
spellingShingle |
Animals Chromosome Mapping Chromosomes Human Pair 8 Disease Models Animal Female Genetic Predisposition to Disease Haplotypes Humans Male Mice Inbred C57BL Molecular Sequence Data Neuregulin-1 Receptor Epidermal Growth Factor 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 Neuregulin 1 and susceptibility to schizophrenia |
topic_facet |
Animals Chromosome Mapping Chromosomes Human Pair 8 Disease Models Animal Female Genetic Predisposition to Disease Haplotypes Humans Male Mice Inbred C57BL Molecular Sequence Data Neuregulin-1 Receptor Epidermal Growth Factor Schizophrenia |
description |
To access full text version of this article. Please click on the hyperlink "View/Open" at the bottom of this page 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. |
author2 |
deCODE Genetics, Reykjavik, Iceland. kstefans@decode.is. |
format |
Article in Journal/Newspaper |
author |
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 |
University of Chicago Press |
publishDate |
2008 |
url |
http://hdl.handle.net/2336/31233 https://doi.org/10.1086/342734 |
genre |
Iceland |
genre_facet |
Iceland |
op_relation |
http://www.sciencedirect.com/science/article/B8JDD-4PYSFD6-J/1/d8488e3081ae23e30a31f6b1ec48865a Am. J. Hum. Genet. 2002, 71(4):877-92 0002-9297 12145742 doi:10.1086/342734 http://hdl.handle.net/2336/31233 American journal of human genetics |
op_doi |
https://doi.org/10.1086/342734 |
container_title |
The American Journal of Human Genetics |
container_volume |
71 |
container_issue |
4 |
container_start_page |
877 |
op_container_end_page |
892 |
_version_ |
1766041309840146432 |