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World J Biol Psychiatry. 2012 Oct;13(7):550-4. doi: 10.3109/15622975.2012.666359. Epub 2012 Mar 5.

Functional investigation of a schizophrenia GWAS signal at the CDC42 gene.

Author information

1
Neuropsychiatric Genetics Research Group, Department of Psychiatry and Institute of Molecular Medicine, Trinity College Dublin, Dublin, Ireland.

Abstract

OBJECTIVES:

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.

PMID:
22385474
DOI:
10.3109/15622975.2012.666359
[Indexed for MEDLINE]

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