Neuropsychological effects of the CSMD1 genome-wide associated schizophrenia risk variant rs10503253.
Authors
Donohoe, GWalters, J
Hargreaves, A
Rose, E J
Morris, D W
Fahey, C
Bellini, S
Cummins, E
Giegling, I
Hartmann, A M
Möller, H-J
Muglia, P
Owen, M J
Gill, M
O'Donovan, M C
Tropea, D
Rujescu, D
Corvin, A
Affiliation
Neuropsychiatric Genetics Group, Department of Psychiatry, Institute of Molecular Medicine, Trinity College Dublin, St. James Hospital, Dublin, Ireland. gary.donohoe@tcd.ieIssue Date
2013-03MeSH
AdolescentAdult
Aged
Alleles
Attention
Brain
Case-Control Studies
Cognition
Genetic Predisposition to Disease
Genome-Wide Association Study
Germany
Humans
Ireland
Membrane Proteins
Memory, Episodic
Middle Aged
Neuropsychological Tests
Phenotype
Polymorphism, Single Nucleotide
Schizophrenia
Metadata
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Neuropsychological effects of the CSMD1 genome-wide associated schizophrenia risk variant rs10503253. 2013, 12 (2):203-9 Genes Brain Behav.Journal
Genes, brain, and behaviorDOI
10.1111/gbb.12016PubMed ID
23320435Abstract
The single-nucleotide polymorphism (SNP) rs10503253, located within the CUB and Sushi multiple domains-1 (CSMD1) gene on 8p23.2, was recently identified as genome-wide significant for schizophrenia (SZ), but is of unknown function. We investigated the neurocognitive effects of this CSMD1 variant in vivo in patients and healthy participants using behavioral and imaging measures of brain structure and function. We compared carriers and non-carriers of the risk 'A' allele on measures of neuropsychological performance typically impaired in SZ (general cognitive ability, episodic and working memory and attentional control) in independent samples of Irish patients (n = 387) and controls (n = 171) and German patients (205) and controls (n = 533). Across these groups, the risk 'A' allele at CSMD1 was associated with deleterious effects across a number of neurocognitive phenotypes. Specifically, the risk allele was associated with poorer performance on neuropsychological measures of general cognitive ability and memory function but not attentional control. These effects, while significant, were subtle, and varied between samples. Consistent with previous evidence suggesting that CSMD1 may be involved in brain mechanisms related to memory and learning, these data appear to reflect the deleterious effects of the identified 'A' risk allele on neurocognitive function, possibly as part of the mechanism by which CSMD1 is associated with SZ risk.Item Type
ArticleLanguage
enISSN
1601-183Xae974a485f413a2113503eed53cd6c53
10.1111/gbb.12016
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