Study Report

Reference	Bass, N. J.,2009 PMID: 19586533
Citation	Bass, N. J., S. R. Datta, et al. (2009). Evidence for the association of the DAOA (G72) gene with schizophrenia and bipolar disorder but not for the association of the DAO gene with schizophrenia. Behav Brain Funct 5: 28.
Disease Type	Bipolar Disorder & Schizophrenia
Study Design	case-control
Study Type	Candidate-gene association study
Sample Size	431 patients with schizophrenia, 303 patients with bipolar disorder and 442 ancestrally matched supernormal controls
SNP/Region/Marker Size	14 SNPs
Predominant Ethnicity	Caucasian
Population	British

Sample Diagnosis	RDC
Sample Status	The case and control samples were recruited from London and South England and consist of 431 volunteers with schizophrenia, 303 volunteers with bipolar disorder and 443 control volunteers. For all groups subjects were included only if three out of four grandparents were of English, Irish, Welsh or Scottish descent.Volunteers were excluded if the other grandparent was of non Caucasian European ancestry (based on the EU countries before the 2004 enlargement). UK National Health Service multicentre and local research ethics approval was obtained and all subjects signed an approved consent form after reading an information sheet. All volunteers with schizophrenia or bipolar disorder were interviewed using the SADS-L. All cases were selected on the basis of having a primary clinical diagnosis of schizophrenia or bipolar disorder and were then formally diagnosed if they achieved the probable level of the Research Diagnostic Criteria (RDC). Research subjects with brain damage prior to the onset of the disorder were excluded. The supernormal control subjects were also interviewed with the initial clinical screening questions of the SADS-L and selected on the basis of not having a family history of schizophrenia, alcoholism or bipolar disorder and for having no personal history of any RDC defined mental disorder.
Technique	genotyping
Statistical Method	Single marker allelic association analyses were performed using standard chi-squared tests. The genotypes were analysed for marker-to-marker linkage disequilibrium (LD) using GENECOUNTING/LDPAIRS. This computes D' and r2 tests of LD and maximum likelihood estimates of haplotype frequencies from phase unknown case control data.The significance of any overall haplotype association was computed using a permutation test.
Result Summary	RESULTS: Ten SNPs spanning the DAOA locus were genotyped in these samples. In addition three SNPs were genotyped at the DAO locus in the schizophrenia sample. Allelic association was detected between the marker rs3918342 (M23), 3' to the DAOA gene and both schizophrenia (chi2 = 5.824 p = 0.016) and bipolar disorder (chi2 = 4.293 p = 0.038). A trend towards association with schizophrenia was observed for two other DAOA markers rs3916967 (M14, chi2 = 3.675 p = 0.055) and rs1421292 (M24; chi2 = 3.499 p = 0.062). A test of association between a three marker haplotype comprising of the SNPs rs778293 (M22), rs3918342 (M23) and rs1421292 (M24) and schizophrenia gave a global empirical significance of p = 0.015. No evidence was found to confirm the association of genetic markers at the DAO gene with schizophrenia. CONCLUSION: Our results provide some support for a role for DAOA in susceptibility to schizophrenia and bipolar disorder.