title: Functional investigation of a schizophrenia GWAS signal at the CDC42 gene.
abstract: OBJECTIVE
  SNP rs2473277 upstream of the cell division cycle 42 (CDC42) gene was associated with schizophrenia in a recent genome-wide association study (GWAS). Reduced expression of CDC42 in schizophrenia has previously been reported. Our objective was to test whether the associated SNP affected CDC42 expression.
  
  
  METHODS
  Two available SNP × gene expression datasets were accessed to test the effect of rs2473277 on CDC42 expression: (i) the mRNA by SNP Browser, which presents results of a genome-wide linkage study of gene expression, and (ii) the Genevar HapMap expression dataset. rs2473277 is in strong linkage disequilibrium (LD) with the SNP rs2473307 (r(2) =0.96), which is predicted to affect transcription factor binding. rs2473307 was directly tested for allelic effects on gene expression using a gene reporter assay in a human neuronal cell line.
  
  
  RESULTS
  In both datasets, the schizophrenia risk allele at rs2473277 was associated with a reduction in CDC42 mRNA levels. In the reporter gene assay the risk allele at rs2473307 similarly reduced gene expression.
  
  
  CONCLUSIONS
  We found evidence that rs2473307, in strong LD with the schizophrenia associated SNP rs2473277, is a functional variant at CDC42 that may increase risk for schizophrenia by reducing expression of CDC42.
authors.affiliation: Neuropsychiatric Genetics Research Group, Department of Psychiatry and Institute of Molecular Medicine, Trinity College Dublin, Dublin, Ireland.
authors.forename: William P
authors.initials: WP
authors.lastname: Gilks
authors.forename: Matthew
authors.initials: M
authors.lastname: Hill
authors.forename: Michael
authors.initials: M
authors.lastname: Gill
authors.forename: Gary
authors.initials: G
authors.lastname: Donohoe
authors.forename: Aiden P
authors.initials: AP
authors.lastname: Corvin
authors.forename: Derek W
authors.initials: DW
authors.lastname: Morris
mesh_terms: D000483:Alleles; D018797:Cell Cycle Proteins / Q000235:genetics*; D030541:Databases, Genetic; D015870:Gene Expression / Q000235:genetics*; D017930:Genes, Reporter / Q000235:genetics; D008040:Genetic Linkage / Q000235:genetics*; D020022:Genetic Predisposition to Disease / Q000235:genetics; D055106:Genome-Wide Association Study / Q000379:methods* / Q000706:statistics & numerical data; D006801:Humans; D015810:Linkage Disequilibrium / Q000235:genetics; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D012333:RNA, Messenger / Q000235:genetics; D012306:Risk; D012559:Schizophrenia / Q000235:genetics*
chemical_list: D018797:Cell Cycle Proteins; C489423:MCM5 protein, human; D012333:RNA, Messenger