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

Nicholas J Bass,David Curtis,Jacob Lawrence,Jonathan Pimm,Hugh Md Gurling,Digby Quested,Srinivasa Thirumalai,Andrew Mcquillin,Susmita R Datta,Vinay Puri,Khalid Choudhury

doi:10.1186/1744-9081-5-28

Abstract

BackgroundPrevious linkage and association studies have implicated the D-amino acid oxidase activator gene (DAOA)/G30 locus or neighbouring region of chromosome 13q33.2 in the genetic susceptibility to both schizophrenia and bipolar disorder. Four single nucleotide polymorphisms (SNPs) within the D-amino acid oxidase (DAO) gene located at 12q24.11 have also been found to show allelic association with schizophrenia.MethodsWe used the case control method to test for genetic association with variants at these loci in a sample of 431 patients with schizophrenia, 303 patients with bipolar disorder and 442 ancestrally matched supernormal controls all selected from the UK population.ResultsTen 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 (χ2 = 5.824 p = 0.016) and bipolar disorder (χ2 = 4.293 p = 0.038). A trend towards association with schizophrenia was observed for two other DAOA markers rs3916967 (M14, χ2 = 3.675 p = 0.055) and rs1421292 (M24; χ2 = 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.ConclusionOur results provide some support for a role for DAOA in susceptibility to schizophrenia and bipolar disorder.

Highlights

The lifetime risk of developing schizophrenia or bipolar disorder in the UK is 0.7% – 0.85% and 0.3% – 1.5% respectively
Replicated evidence from genetic linkage studies has confirmed that multiple chromosomal loci are involved in the heritability of both bipolar disorder and schizophrenia [2,3]
Sample 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 Genotyping Eleven single nucleotide polymorphisms (SNPs) at the D-amino acid oxidase activator gene (DAOA) locus were genotyped in the BPD, schizophrenia and control samples

Summary

Introduction

The lifetime risk of developing schizophrenia or bipolar disorder in the UK is 0.7% – 0.85% and 0.3% – 1.5% respectively. Evidence that a schizophrenia susceptibility locus maps to chromosome 13q has been reported by several groups [411], not consistently demonstrated [2,12,13]. Such variability in the outcome of linkage studies is to be expected given genetic heterogeneity. Previous linkage and association studies have implicated the D-amino acid oxidase activator gene (DAOA)/G30 locus or neighbouring region of chromosome 13q33.2 in the genetic susceptibility to both schizophrenia and bipolar disorder. Four single nucleotide polymorphisms (SNPs) within the D-amino acid oxidase (DAO) gene located at 12q24.11 have been found to show allelic association with schizophrenia

Methods

Results

Conclusion