title: Association of a risk allele of ANK3 with cognitive performance and cortical thickness in patients with first-episode psychosis.
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.
  
  
  CONCLUSIONS
  The sample size is modest given that a low-frequency variant was being examined.
  
  
  CONCLUSIONS
  The ANK3 risk allele rs1938526 appears to be associated with general cognitive impairment and widespread cortical thinning in patients with FEP.
authors.affiliation: Douglas Mental Health University Institute, Montréal, Que., Canada.
authors.forename: Clifford
authors.initials: C
authors.lastname: Cassidy
authors.affiliation: Douglas Mental Health University Institute, Montréal, Que., Canada.
authors.forename: Lisa
authors.initials: L
authors.lastname: Buchy
authors.affiliation: Douglas Mental Health University Institute, Montréal, Que., Canada.
authors.forename: Michael
authors.initials: M
authors.lastname: Bodnar
authors.affiliation: Douglas Mental Health University Institute, Montréal, Que., Canada.
authors.forename: Jennifer
authors.initials: J
authors.lastname: Dell'elce
authors.affiliation: Douglas Mental Health University Institute, Montréal, Que., Canada.
authors.forename: Zia
authors.initials: Z
authors.lastname: Choudhry
authors.affiliation: Douglas Mental Health University Institute, Montréal, Que., Canada.
authors.forename: Ferid
authors.initials: F
authors.lastname: Fathalli
authors.affiliation: Douglas Mental Health University Institute, Montréal, Que., Canada.
authors.forename: Sarojini
authors.initials: S
authors.lastname: Sengupta
authors.affiliation: Douglas Mental Health University Institute, Montréal, Que., Canada.
authors.forename: Rebecca
authors.initials: R
authors.lastname: Fox
authors.affiliation: Douglas Mental Health University Institute, and Department of Psychiatry, McGill University, Montréal, Que., Canada.
authors.forename: Ashok
authors.initials: A
authors.lastname: Malla
authors.affiliation: Douglas Mental Health University Institute, and Department of Psychiatry, McGill University, Montréal, Que., Canada.
authors.forename: Martin
authors.initials: M
authors.lastname: Lepage
authors.affiliation: Douglas Mental Health University Institute, Montréal, Que., Canada.
authors.forename: Srividya
authors.initials: S
authors.lastname: Iyer
authors.affiliation: Douglas Mental Health University Institute, and Department of Psychiatry, McGill University, Montréal, Que., Canada.
authors.forename: Ridha
authors.initials: R
authors.lastname: Joober
mesh_terms: D000293:Adolescent; D000328:Adult; D000483:Alleles; D017487:Ankyrins / Q000235:genetics*; D001921:Brain / Q000473:pathology; D002540:Cerebral Cortex / Q000473:pathology*; D003072:Cognition Disorders / Q000150:complications / Q000235:genetics* / Q000473:pathology*; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D060005:Genotyping Techniques; D006801:Humans; D015810:Linkage Disequilibrium; D008279:Magnetic Resonance Imaging; D008297:Male; D009483:Neuropsychological Tests; D009929:Organ Size; D020641:Polymorphism, Single Nucleotide; D011618:Psychotic Disorders / Q000150:complications / Q000235:genetics* / Q000473:pathology*; D012306:Risk; D055815:Young Adult
chemical_list: C490613:ANK3 protein, human; D017487:Ankyrins
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