The DISC1 Pathway in the Genetic Etiology of Schizophrenia
Schizophrenia is a severe psychotic disorder affecting 0.5-1 % of the population. The disorder is characterized by hallucinations; delusions; disorganized behavior and speech; avolition; anhedonia; flattened affect and cognitive deficits. The etiology of the disorder is complex with evidence for mul...
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Helsingin yliopisto
2010
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ftunivhelsihelda:oai:helda.helsinki.fi:10138/20485 2023-08-20T04:08:44+02:00 The DISC1 Pathway in the Genetic Etiology of Schizophrenia Tomppo, Liisa Korth, Carsten University of Helsinki, Faculty of Medicine, Haartman Institute, Medical Genetics Institute for Molecular Medicine Finland FIMM, National Institute for Health and Welfare Helsingin yliopisto, lääketieteellinen tiedekunta, kliinisteoreettinen laitos Helsingfors universitet, medicinska fakulteten, Haartman institutet Peltonen-Palotie, Leena Hennah, William 2010-11-25T11:26:45Z application/pdf http://hdl.handle.net/10138/20485 eng eng Helsingin yliopisto Helsingfors universitet University of Helsinki URN:ISBN:978-952-245-315-0 http://hdl.handle.net/10138/20485 URN:ISBN:978-952-245-316-7 Julkaisu on tekijänoikeussäännösten alainen. Teosta voi lukea ja tulostaa henkilökohtaista käyttöä varten. Käyttö kaupallisiin tarkoituksiin on kielletty. This publication is copyrighted. You may download, display and print it for Your own personal use. Commercial use is prohibited. Publikationen är skyddad av upphovsrätten. Den får läsas och skrivas ut för personligt bruk. Användning i kommersiellt syfte är förbjuden. genetiikka Text Doctoral dissertation (article-based) Artikkeliväitöskirja Artikelavhandling doctoralThesis 2010 ftunivhelsihelda 2023-07-28T06:26:30Z Schizophrenia is a severe psychotic disorder affecting 0.5-1 % of the population. The disorder is characterized by hallucinations; delusions; disorganized behavior and speech; avolition; anhedonia; flattened affect and cognitive deficits. The etiology of the disorder is complex with evidence for multiple genes contributing to the onset of the disorder along with environmental factors. DISC1 is one of the most promising candidate genes for schizophrenia. It codes for a protein which takes part in numerous molecular interactions along several pathways. This network, termed as the DISC1 pathway, is evidently important for the development and maturation of the central nervous system from the embryo until young adulthood. Disruption at these pathways is thought to predispose schizophrenia. In the present study, we have studied the DISC1 pathway in the etiology of schizophrenia in the Finnish population. We have utilized large Finnish samples; the schizophrenia family sample where DISC1 was originally shown to associate with schizophrenia and the Northern Finland birth cohort 1966 (NFBC66). Several DISC1 binding partners displayed evidence for association in the family sample along with DISC1. Through a genome-wide linkage study, we found a significant linkage signal to a locus where a DISC1 binding partner NDE1 is located at the carriers of a certain DISC1 risk variant. In a follow-up study, genetic markers in NDE1 displayed significant evidence for association with schizophrenia. Further exploration of association between 11 genes of the DISC1 pathway and schizophrenia led to recognition of novel variants in NDEL1, PDE4B and PDE4D that significantly either increased or decreased the risk for schizophrenia. Further, we found evidence that DISC1 itself has a significant role in the human mental functioning even in the healthy population. Variants in DISC1 had a significant effect on anhedonia which is a trait present at everybody but is in its severe form one of the main symptoms of schizophrenia and correlates with ... Doctoral or Postdoctoral Thesis Northern Finland Helsingfors Universitet: HELDA – Helsingin yliopiston digitaalinen arkisto |
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Helsingfors Universitet: HELDA – Helsingin yliopiston digitaalinen arkisto |
op_collection_id |
ftunivhelsihelda |
language |
English |
topic |
genetiikka |
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genetiikka Tomppo, Liisa The DISC1 Pathway in the Genetic Etiology of Schizophrenia |
topic_facet |
genetiikka |
description |
Schizophrenia is a severe psychotic disorder affecting 0.5-1 % of the population. The disorder is characterized by hallucinations; delusions; disorganized behavior and speech; avolition; anhedonia; flattened affect and cognitive deficits. The etiology of the disorder is complex with evidence for multiple genes contributing to the onset of the disorder along with environmental factors. DISC1 is one of the most promising candidate genes for schizophrenia. It codes for a protein which takes part in numerous molecular interactions along several pathways. This network, termed as the DISC1 pathway, is evidently important for the development and maturation of the central nervous system from the embryo until young adulthood. Disruption at these pathways is thought to predispose schizophrenia. In the present study, we have studied the DISC1 pathway in the etiology of schizophrenia in the Finnish population. We have utilized large Finnish samples; the schizophrenia family sample where DISC1 was originally shown to associate with schizophrenia and the Northern Finland birth cohort 1966 (NFBC66). Several DISC1 binding partners displayed evidence for association in the family sample along with DISC1. Through a genome-wide linkage study, we found a significant linkage signal to a locus where a DISC1 binding partner NDE1 is located at the carriers of a certain DISC1 risk variant. In a follow-up study, genetic markers in NDE1 displayed significant evidence for association with schizophrenia. Further exploration of association between 11 genes of the DISC1 pathway and schizophrenia led to recognition of novel variants in NDEL1, PDE4B and PDE4D that significantly either increased or decreased the risk for schizophrenia. Further, we found evidence that DISC1 itself has a significant role in the human mental functioning even in the healthy population. Variants in DISC1 had a significant effect on anhedonia which is a trait present at everybody but is in its severe form one of the main symptoms of schizophrenia and correlates with ... |
author2 |
Korth, Carsten University of Helsinki, Faculty of Medicine, Haartman Institute, Medical Genetics Institute for Molecular Medicine Finland FIMM, National Institute for Health and Welfare Helsingin yliopisto, lääketieteellinen tiedekunta, kliinisteoreettinen laitos Helsingfors universitet, medicinska fakulteten, Haartman institutet Peltonen-Palotie, Leena Hennah, William |
format |
Doctoral or Postdoctoral Thesis |
author |
Tomppo, Liisa |
author_facet |
Tomppo, Liisa |
author_sort |
Tomppo, Liisa |
title |
The DISC1 Pathway in the Genetic Etiology of Schizophrenia |
title_short |
The DISC1 Pathway in the Genetic Etiology of Schizophrenia |
title_full |
The DISC1 Pathway in the Genetic Etiology of Schizophrenia |
title_fullStr |
The DISC1 Pathway in the Genetic Etiology of Schizophrenia |
title_full_unstemmed |
The DISC1 Pathway in the Genetic Etiology of Schizophrenia |
title_sort |
disc1 pathway in the genetic etiology of schizophrenia |
publisher |
Helsingin yliopisto |
publishDate |
2010 |
url |
http://hdl.handle.net/10138/20485 |
genre |
Northern Finland |
genre_facet |
Northern Finland |
op_relation |
URN:ISBN:978-952-245-315-0 http://hdl.handle.net/10138/20485 URN:ISBN:978-952-245-316-7 |
op_rights |
Julkaisu on tekijänoikeussäännösten alainen. Teosta voi lukea ja tulostaa henkilökohtaista käyttöä varten. Käyttö kaupallisiin tarkoituksiin on kielletty. This publication is copyrighted. You may download, display and print it for Your own personal use. Commercial use is prohibited. Publikationen är skyddad av upphovsrätten. Den får läsas och skrivas ut för personligt bruk. Användning i kommersiellt syfte är förbjuden. |
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1774721187067199488 |