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Sequencing of DISC1...
Sequencing of DISC1 Pathway Genes Reveals Increased Burden of Rare Missense Variants in Schizophrenia Patients from a Northern Swedish Population
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- Moens, Lotte N (author)
- Applied Molecular Genomics Group, Department of Molecular Genetics, Flanders Institute for Biotechnology (VIB), Flanders, Belgium; University of Antwerp (UA), Antwerp, Belgium
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- De Rijk, Peter (author)
- Applied Molecular Genomics Group, Department of Molecular Genetics, Flanders Institute for Biotechnology (VIB), Flanders, Belgium; University of Antwerp (UA), Antwerp, Belgium
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- Reumers, Joke (author)
- SWITCH Laboratory, Flanders Institute for Biotechnology (VIB), Flanders, Belgium; Vrije Universiteit Brussel (VUB), Brussels, Belgium
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- Van den Bossche, Maarten J. A. (author)
- Applied Molecular Genomics Group, Department of Molecular Genetics, Flanders Institute for Biotechnology (VIB), Flanders, Belgium; University of Antwerp (UA), Antwerp, Belgium
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- Glassee, Wim (author)
- Applied Molecular Genomics Group, Department of Molecular Genetics, Flanders Institute for Biotechnology (VIB), Flanders, Belgium; University of Antwerp (UA), Antwerp, Belgium
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- De Zutter, Sonia (author)
- Applied Molecular Genomics Group, Department of Molecular Genetics, Flanders Institute for Biotechnology (VIB), Flanders, Belgium; University of Antwerp (UA), Antwerp, Belgium
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- Lenaerts, An-Sofie (author)
- Applied Molecular Genomics Group, Department of Molecular Genetics, Flanders Institute for Biotechnology (VIB), Flanders, Belgium; University of Antwerp (UA), Antwerp, Belgium
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- Nordin, Annelie (author)
- Umeå universitet,Psykiatri
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- Nilsson, Lars-Göran (author)
- Stockholms universitet,Psykologiska institutionen,Department of Psychology, Stockholm University, Stockholm, Sweden
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- Castello, Ignacio Medina (author)
- Functional Genomics Unit, Bioinformatics and Genomics Department, Prince Felipe Research Centre (CIPF), Valencia, Spain
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- Norrback, Karl-Fredrik (author)
- Umeå universitet,Psykiatri
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- Goossens, Dirk (author)
- Applied Molecular Genomics Group, Department of Molecular Genetics, Flanders Institute for Biotechnology (VIB), Flanders, Belgium; University of Antwerp (UA), Antwerp, Belgium
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- Van Steen, Kristel (author)
- Systems and Modeling Unit, Montefiore Institute/GIGA, University of Liège, Liège, Belgium
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- Adolfsson, Rolf (author)
- Umeå universitet,Psykiatri
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- Del-Favero, Jurgen (author)
- Applied Molecular Genomics Group, Department of Molecular Genetics, Flanders Institute for Biotechnology (VIB), Flanders, Belgium; University of Antwerp (UA), Antwerp, Belgium
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(creator_code:org_t)
- 2011-08-11
- 2011
- English.
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In: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 6:8, s. e23450-
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https://doi.org/10.1...
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https://umu.diva-por... (primary) (Raw object)
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https://urn.kb.se/re...
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https://doi.org/10.1...
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Abstract
Subject headings
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- In recent years, DISC1 has emerged as one of the most credible and best supported candidate genes for schizophrenia and related neuropsychiatric disorders. Furthermore, increasing evidence - both genetic and functional - indicates that many of its protein interaction partners are also involved in the development of these diseases. In this study, we applied a pooled sample 454 sequencing strategy, to explore the contribution of genetic variation in DISC1 and 10 of its interaction partners (ATF5, Grb2, FEZ1, LIS-1, PDE4B, NDE1, NDEL1, TRAF3IP1, YWHAE, and ZNF365) to schizophrenia susceptibility in an isolated northern Swedish population. Mutation burden analysis of the identified variants in a population of 486 SZ patients and 514 control individuals, revealed that non-synonymous rare variants with a MAF<0.01 were significantly more present in patients compared to controls (8.64% versus 4.7%, P = 0.018), providing further evidence for the involvement of DISC1 and some of its interaction partners in psychiatric disorders. This increased burden of rare missense variants was even more striking in a subgroup of early onset patients (12.9% versus 4.7%, P = 0.0004), highlighting the importance of studying subgroups of patients and identifying endophenotypes. Upon investigation of the potential functional effects associated with the identified missense variants, we found that similar to 90% of these variants reside in intrinsically disordered protein regions. The observed increase in mutation burden in patients provides further support for the role of the DISC1 pathway in schizophrenia. Furthermore, this study presents the first evidence supporting the involvement of mutations within intrinsically disordered protein regions in the pathogenesis of psychiatric disorders. As many important biological functions depend directly on the disordered state, alteration of this disorder in key pathways may represent an intriguing new disease mechanism for schizophrenia and related neuropsychiatric diseases. Further research into this unexplored domain will be required to elucidate the role of the identified variants in schizophrenia etiology.
Subject headings
- SAMHÄLLSVETENSKAP -- Psykologi (hsv//swe)
- SOCIAL SCIENCES -- Psychology (hsv//eng)
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinsk bioteknologi -- Biomedicinsk laboratorievetenskap/teknologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Medical Biotechnology -- Biomedical Laboratory Science/Technology (hsv//eng)
- NATURVETENSKAP -- Biologi (hsv//swe)
- NATURAL SCIENCES -- Biological Sciences (hsv//eng)
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine (hsv//eng)
Keyword
- DISC1
- schizophrenia
- Psychology
- Psykologi
- Psychology
- psykologi
- Pathology
Publication and Content Type
- ref (subject category)
- art (subject category)
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- By the author/editor
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Moens, Lotte N
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De Rijk, Peter
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Reumers, Joke
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Van den Bossche, ...
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Glassee, Wim
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De Zutter, Sonia
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Lenaerts, An-Sof ...
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Nordin, Annelie
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Nilsson, Lars-Gö ...
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Castello, Ignaci ...
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Norrback, Karl-F ...
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Goossens, Dirk
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Van Steen, Krist ...
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Adolfsson, Rolf
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Del-Favero, Jurg ...
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- About the subject
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- SOCIAL SCIENCES
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SOCIAL SCIENCES
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and Psychology
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- MEDICAL AND HEALTH SCIENCES
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MEDICAL AND HEAL ...
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and Medical Biotechn ...
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and Biomedical Labor ...
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- NATURAL SCIENCES
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NATURAL SCIENCES
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and Biological Scien ...
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- MEDICAL AND HEALTH SCIENCES
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MEDICAL AND HEAL ...
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and Basic Medicine
- Articles in the publication
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PLOS ONE
- By the university
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Stockholm University
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Umeå University
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Uppsala University