Association of a risk allele of ANK3 with cognitive performance and cortical thickness in patients with first-episode psychosis.

TitleAssociation of a risk allele of ANK3 with cognitive performance and cortical thickness in patients with first-episode psychosis.
Publication TypeJournal Article
Year of Publication2014
AuthorsCassidy C, Buchy L, Bodnar M, Dell'elce J, Choudhry Z, Fathalli F, Sengupta S, Fox R, Malla A, Lepage M, Iyer SN, Joober R
JournalJ Psychiatry Neurosci
Volume39
Issue1
Pagination31-9
Date Published2014 Jan
ISSN1488-2434
KeywordsAdolescent, Adult, Alleles, Ankyrins, Brain, Cerebral Cortex, Cognition Disorders, Female, Gene Frequency, Genetic Predisposition to Disease, Genotyping Techniques, Humans, Linkage Disequilibrium, Magnetic Resonance Imaging, Male, Neuropsychological Tests, Organ Size, Polymorphism, Single Nucleotide, Psychotic Disorders, Risk, Young Adult
Abstract

BACKGROUND: The gene ANK3 is implicated in bipolar disorder and schizophrenia. The present study investigated the influence of this gene on cognitive performance and brain structure among individuals with first-episode psychosis (FEP). The brief illness duration of an FEP sample makes it well suited for studying the effects of genetic variation.METHODS: We genotyped 2 single nucleotide polymorphisms (SNPs; rs1938526 and rs10994336) in ANK3 in patients with FEP. Multivariate analysis of variance compared risk allele carriers and noncarriers on 6 domains of cognition consistent with MATRICS consensus. A subsample of 82 patients was assessed using magnetic resonance imaging. We compared brain structure between carriers and noncarriers using cortical thickness analysis and voxel-based morphometry on white matter.RESULTS: In the 173 patients with FEP included in our study, rs1938526 and rs10994336 were in very high linkage disequilibrium (d' = 0.95), and analyses were therefore only carried out on the SNP (rs1938526) with the highest minor allele frequency (G). Allele G of rs1938526, was associated with lower cognitive performance across domains (F6,164 = 2.38, p = 0.030) and significantly lower scores on the domains of verbal memory (p = 0.015), working memory (p = 0.006) and attention (p = 0.019). The significant effects of this SNP on cognition were not maintained when controlling for IQ. Cortical thinning was observed in risk allele carriers at diverse sites across cortical lobes bilaterally at a threshold of p < 0.01, false discovery rate-corrected. Risk-allele carriers did not show any regions of reduced white matter volume.LIMITATIONS: The sample size is modest given that a low-frequency variant was being examined.CONCLUSION: The ANK3 risk allele rs1938526 appears to be associated with general cognitive impairment and widespread cortical thinning in patients with FEP.

DOI10.1503/jpn.120242
Alternate JournalJ Psychiatry Neurosci
PubMed ID24016415
PubMed Central IDPMC3868663
Grant List / / Canadian Institutes of Health Research / Canada