Molecular Psychiatry Laboratory, Research Department of Mental Health Sciences, University College London Medical School, Windeyer Institute of Medical Sciences, 46 Cleveland Street, London, W1T 4JF, UK.
Behav Brain Funct. 2009 Jul 8;5:28. doi: 10.1186/1744-9081-5-28.
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 also been found to show allelic association with schizophrenia.
We 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.
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.
Our results provide some support for a role for DAOA in susceptibility to schizophrenia and bipolar disorder.
先前的连锁和关联研究表明，D-氨基酸氧化酶激活基因（DAOA）/G30 基因座或 13q33.2 染色体的邻近区域与精神分裂症和双相情感障碍的遗传易感性有关。在位于 12q24.11 的 D-氨基酸氧化酶（DAO）基因内发现的四个单核苷酸多态性（SNP）也显示与精神分裂症的等位基因关联。
我们使用病例对照方法，在来自英国人群的 431 名精神分裂症患者、303 名双相情感障碍患者和 442 名遗传正常对照样本中，测试这些基因座变异的遗传相关性。
在这些样本中，对跨越 DAOA 基因座的 10 个 SNP 进行了基因分型。此外，在精神分裂症样本中还对 DAO 基因座的三个 SNP 进行了基因分型。标记物 rs3918342（M23）与 DAOA 基因 3'端之间的等位基因关联在精神分裂症（chi2 = 5.824，p = 0.016）和双相情感障碍（chi2 = 4.293，p = 0.038）中均有检测到。另外两个 DAOA 标记物 rs3916967（M14，chi2 = 3.675，p = 0.055）和 rs1421292（M24；chi2 = 3.499，p = 0.062）与精神分裂症呈关联趋势。包含 SNP rs778293（M22）、rs3918342（M23）和 rs1421292（M24）的三个标记物单倍型与精神分裂症之间的关联检验给出了一个整体经验显著性 p = 0.015。没有证据证实 DAO 基因的遗传标记与精神分裂症有关。
我们的结果为 DAOA 在精神分裂症和双相情感障碍易感性中的作用提供了一些支持。
