Cardiff University | Prifysgol Caerdydd ORCA
Online Research @ Cardiff 
WelshClear Cookie - decide language by browser settings

The one and the many: effects of the cell adhesion molecule pathway on neuropsychological function in psychosis

Hargreaves, A., Anney, Richard, O'Dushlaine, C., Nicodemus, K. K., Gill, M., Corvin, A., Morris, D. and Donohoe, Gary 2014. The one and the many: effects of the cell adhesion molecule pathway on neuropsychological function in psychosis. Psychological Medicine 44 (10) , pp. 2177-2187. 10.1017/S0033291713002663

Full text not available from this repository.

Abstract

BACKGROUND: Genetic studies of single gene variants have been criticized as providing a simplistic characterization of the genetic basis of illness risk that ignores the effects of other variants within the same biological pathways. Of candidate biological pathways for schizophrenia (SZ), the cell adhesion molecule (CAM) pathway has repeatedly been linked to both psychosis and neurocognitive dysfunction. Here we tested, using risk allele scores derived from the Schizophrenia Psychiatric Genome-Wide Association Study Consortium (PGC-SCZ), whether alleles within the CAM pathway were correlated with poorer neuropsychological function in patients. METHOD: In total, 424 patients with psychosis were assessed in areas of cognitive ability typically found to be impaired in SZ: intelligence quotient, memory, working memory and attentional control. CAM pathway genes were identified using the Kyoto Encyclopedia of Genes and Genomes (KEGG) database. Alleles within these genes identified as significantly associated with SZ risk in the PGC-SCZ were then used to calculate a CAM pathway-based polygenic risk allele score for each patient and these scores were tested for association with cognitive ability. RESULTS: Increased CAM pathway polygenic risk scores were significantly associated with poorer performance on measures of memory and attention, explaining 1-3% of variation on these measures. Notably, the most strongly associated single nucleotide polymorphism (SNP) in the CAM pathway (rs9272105 within HLA-DQA1) explained a similar amount of variance in attentional control, but not memory, as the polygenic risk analysis. CONCLUSIONS: These data support a role for the CAM pathway in cognitive function, both at the level of individual SNPs and the wider pathway. In so doing these data highlight the value of pathway-based polygenic risk score studies as well as single gene studies for understanding SZ-associated deficits in cognition.

Item Type: Article
Date Type: Publication
Status: Published
Schools: MRC Centre for Neuropsychiatric Genetics and Genomics (CNGG)
Medicine
Subjects: R Medicine > R Medicine (General)
Uncontrolled Keywords: Cell adhesion molecules; cognition; gene; HLA-DQA1 ; pathway; psychosis; schizophrenia
Publisher: Cambridge University Press
ISSN: 0033-2917
Date of Acceptance: 21 September 2013
Last Modified: 31 May 2019 12:40
URI: http://orca.cf.ac.uk/id/eprint/85215

Citation Data

Cited 6 times in Scopus. View in Scopus. Powered By Scopus® Data

Actions (repository staff only)

Edit Item Edit Item