Neural effects of the CSMD1 genome-wide associated schizophrenia risk variant rs10503253.

Hdl Handle:
http://hdl.handle.net/10147/323864
Title:
Neural effects of the CSMD1 genome-wide associated schizophrenia risk variant rs10503253.
Authors:
Rose, Emma J; Morris, Derek W; Hargreaves, April; Fahey, Ciara; Greene, Ciara; Garavan, Hugh; Gill, Michael; Corvin, Aiden; Donohoe, Gary
Affiliation:
Neuropsychiatric Genetics Group and Department of Psychiatry, Institute of Molecular Medicine, Trinity College Dublin, St. James Hospital, Dublin, Ireland.
Citation:
Rose EJ et al. Neural effects of the CSMD1 genome-wide associated schizophrenia risk variant rs10503253. Am. J. Med. Genet. B Neuropsychiatr. Genet. 2013, 162B (6):530-7
Journal:
American journal of medical genetics. Part B, Neuropsychiatric genetics : the official publication of the International Society of Psychiatric Genetics
Issue Date:
Sep-2013
URI:
http://hdl.handle.net/10147/323864
DOI:
10.1002/ajmg.b.32182
PubMed ID:
23839771
Abstract:
The single nucleotide polymorphism rs10503253 within the CUB and Sushi multiple domains-1 (CSMD1) gene on 8p23.2 has been identified as genome-wide significant for schizophrenia (SZ). This gene is of unknown function but has been implicated in multiple neurodevelopmental disorders that impact upon cognition, leading us to hypothesize that an effect on brain structure and function underlying cognitive processes may be part of the mechanism by which CMSD1 increases illness risk. To test this hypothesis, we investigated this CSMD1 variant in vivo in healthy participants in a magnetic resonance imaging (MRI) study comprised of both fMRI of spatial working memory (N = 50) and a voxel-based morphometry investigation of grey and white matter (WM) volume (N = 150). Analyses of these data indicated that the risk "A" allele was associated with comparatively reduced cortical activations in BA18, that is, middle occipital gyrus and cuneus; posterior brain regions that support maintenance processes during performance of a spatial working memory task. Conversely, there was an absence of significant structural differences in brain volume (i.e., grey or WM). In accordance with previous evidence, these data suggest that CSMD1 may mediate brain function related to cognitive processes (i.e., executive function); with the relatively deleterious effects of the identified "A" risk allele on brain activity possibly constituting part of the mechanism by which CSMD1 increases schizophrenia risk.
Item Type:
Article
Language:
en
Keywords:
SCHIZOPHRENIA; GENETICS
MeSH:
Adult; Brain Mapping; Case-Control Studies; Cognition Disorders; Female; Genetic Predisposition to Disease; Genome-Wide Association Study; Humans; Magnetic Resonance Imaging; Male; Membrane Proteins; Neuropsychological Tests; Polymorphism, Single Nucleotide; Prognosis; Risk Factors; Schizophrenia; Young Adult
ISSN:
1552-485X

Full metadata record

DC FieldValue Language
dc.contributor.authorRose, Emma Jen_GB
dc.contributor.authorMorris, Derek Wen_GB
dc.contributor.authorHargreaves, Aprilen_GB
dc.contributor.authorFahey, Ciaraen_GB
dc.contributor.authorGreene, Ciaraen_GB
dc.contributor.authorGaravan, Hughen_GB
dc.contributor.authorGill, Michaelen_GB
dc.contributor.authorCorvin, Aidenen_GB
dc.contributor.authorDonohoe, Garyen_GB
dc.date.accessioned2014-07-29T08:34:45Z-
dc.date.available2014-07-29T08:34:45Z-
dc.date.issued2013-09-
dc.identifier.citationRose EJ et al. Neural effects of the CSMD1 genome-wide associated schizophrenia risk variant rs10503253. Am. J. Med. Genet. B Neuropsychiatr. Genet. 2013, 162B (6):530-7en_GB
dc.identifier.issn1552-485X-
dc.identifier.pmid23839771-
dc.identifier.doi10.1002/ajmg.b.32182-
dc.identifier.urihttp://hdl.handle.net/10147/323864-
dc.description.abstractThe single nucleotide polymorphism rs10503253 within the CUB and Sushi multiple domains-1 (CSMD1) gene on 8p23.2 has been identified as genome-wide significant for schizophrenia (SZ). This gene is of unknown function but has been implicated in multiple neurodevelopmental disorders that impact upon cognition, leading us to hypothesize that an effect on brain structure and function underlying cognitive processes may be part of the mechanism by which CMSD1 increases illness risk. To test this hypothesis, we investigated this CSMD1 variant in vivo in healthy participants in a magnetic resonance imaging (MRI) study comprised of both fMRI of spatial working memory (N = 50) and a voxel-based morphometry investigation of grey and white matter (WM) volume (N = 150). Analyses of these data indicated that the risk "A" allele was associated with comparatively reduced cortical activations in BA18, that is, middle occipital gyrus and cuneus; posterior brain regions that support maintenance processes during performance of a spatial working memory task. Conversely, there was an absence of significant structural differences in brain volume (i.e., grey or WM). In accordance with previous evidence, these data suggest that CSMD1 may mediate brain function related to cognitive processes (i.e., executive function); with the relatively deleterious effects of the identified "A" risk allele on brain activity possibly constituting part of the mechanism by which CSMD1 increases schizophrenia risk.en_GB
dc.language.isoenen
dc.rightsArchived with thanks to American journal of medical genetics. Part B, Neuropsychiatric genetics : the official publication of the International Society of Psychiatric Geneticsen_GB
dc.subjectSCHIZOPHRENIAen_GB
dc.subjectGENETICSen_GB
dc.subject.meshAdult-
dc.subject.meshBrain Mapping-
dc.subject.meshCase-Control Studies-
dc.subject.meshCognition Disorders-
dc.subject.meshFemale-
dc.subject.meshGenetic Predisposition to Disease-
dc.subject.meshGenome-Wide Association Study-
dc.subject.meshHumans-
dc.subject.meshMagnetic Resonance Imaging-
dc.subject.meshMale-
dc.subject.meshMembrane Proteins-
dc.subject.meshNeuropsychological Tests-
dc.subject.meshPolymorphism, Single Nucleotide-
dc.subject.meshPrognosis-
dc.subject.meshRisk Factors-
dc.subject.meshSchizophrenia-
dc.subject.meshYoung Adult-
dc.titleNeural effects of the CSMD1 genome-wide associated schizophrenia risk variant rs10503253.en_GB
dc.typeArticleen
dc.contributor.departmentNeuropsychiatric Genetics Group and Department of Psychiatry, Institute of Molecular Medicine, Trinity College Dublin, St. James Hospital, Dublin, Ireland.en_GB
dc.identifier.journalAmerican journal of medical genetics. Part B, Neuropsychiatric genetics : the official publication of the International Society of Psychiatric Geneticsen_GB
dc.description.fundingNo fundingen
dc.description.provinceLeinsteren
dc.description.peer-reviewpeer-reviewen

Related articles on PubMed

All Items in Lenus, The Irish Health Repository are protected by copyright, with all rights reserved, unless otherwise indicated.