title: The CSMD1 genome-wide associated schizophrenia risk variant rs10503253 affects general cognitive ability and executive function in healthy males.
abstract: BACKGROUND
  The single-nucleotide polymorphism (SNP) rs10503253, located within the CUB and Sushi multiple domains-1 (CSMD1) gene on 8p23.2, has reached genome-wide support as a risk factor for schizophrenia. There is initial but inconclusive evidence for a role of this variant in aspects of cognition.
  
  
  METHODS
  We investigated the neurocognitive effects of the CSMD1 rs10503253 (C/A) polymorphism in a large, demographically homogeneous sample of young, healthy Greek Caucasian males (n=1149) phenotyped for a wide range of neuropsychological measures, most of which have been shown to be reliable endophenotypes for schizophrenia.
  
  
  RESULTS
  The risk 'A' allele was associated with poorer performance on measures of general cognitive ability, strategy formation, spatial and visual working memory, set shifting, target detection and planning for problem solving but not for emotional decision making. Most of these effects were dependent on risk "A" allele dose, with AA and CC homozygotes being the worse and the best respectively, while CA individuals were intermediate. Potential genotype effects in Stroop and verbal memory performance were also suggested by our dataset.
  
  
  CONCLUSIONS
  These results underline the relevance of the risk "A" allele to neurocognitive functioning and suggest that its detrimental effects on cognition, may be part of the mechanism by which the CSMD1 mediates risk for schizophrenia.
authors.affiliation: Department of Psychiatry, Faculty of Medicine, University of Crete, Heraklion, Crete, Greece.
authors.forename: Erasmia
authors.initials: E
authors.lastname: Koiliari
authors.affiliation: Department of Psychiatry, Mount Sinai, New York, NY, USA; Department of Genetics and Genomic Science, Institute for Multiscale Biology, Mount Sinai, New York, NY, USA; Mental Illness Research, Education, and Clinical Center (VISN 3), James J. Peters VA Medical Center, Bronx, NY, USA.
authors.forename: Panos
authors.initials: P
authors.lastname: Roussos
authors.affiliation: Department of Psychiatry, Faculty of Medicine, University of Crete, Heraklion, Crete, Greece.
authors.forename: Emmanouil
authors.initials: E
authors.lastname: Pasparakis
authors.affiliation: Division of Psychiatry Research, The Zucker Hillside Hospital, Glen Oaks, NY, USA; Feinstein Institute for Medical Research, Manhasset, NY, USA.
authors.forename: Todd
authors.initials: T
authors.lastname: Lencz
authors.affiliation: Division of Psychiatry Research, The Zucker Hillside Hospital, Glen Oaks, NY, USA; Feinstein Institute for Medical Research, Manhasset, NY, USA.
authors.forename: Anil
authors.initials: A
authors.lastname: Malhotra
authors.affiliation: Department of Psychiatry, Mount Sinai, New York, NY, USA; Mental Illness Research, Education, and Clinical Center (VISN 3), James J. Peters VA Medical Center, Bronx, NY, USA.
authors.forename: Larry J
authors.initials: LJ
authors.lastname: Siever
authors.affiliation: Department of Psychology, University of Crete, Rethymno, Crete, Greece.
authors.forename: Stella G
authors.initials: SG
authors.lastname: Giakoumaki
authors.affiliation: Department of Psychiatry, Faculty of Medicine, University of Crete, Heraklion, Crete, Greece. Electronic address: pbitsios@med.uoc.gr.
authors.forename: Panos
authors.initials: P
authors.lastname: Bitsios
mesh_terms: D000293:Adolescent; D000328:Adult; D000483:Alleles; D003071:Cognition; D056344:Executive Function; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study; D060005:Genotyping Techniques; D006115:Greece; D006801:Humans; D007361:Intelligence Tests; D008297:Male; D008565:Membrane Proteins / Q000235:genetics*; D009483:Neuropsychological Tests; D020641:Polymorphism, Single Nucleotide; D012307:Risk Factors; D012559:Schizophrenia / Q000235:genetics*; D012565:Schizophrenic Psychology; D025521:Tumor Suppressor Proteins; D044465:White People / Q000235:genetics; D055815:Young Adult
chemical_list: C477880:CSMD1 protein, human; D008565:Membrane Proteins; D025521:Tumor Suppressor Proteins
keywords: CSMD1 gene; Cognition; Endophenotypes; Executive function; Schizophrenia