Abstract
BackgroundThe DAOA/G30 (D-amino acid oxidase activator) gene complex at chromosomal region 13q32-33 is one of the most intriguing susceptibility loci for the major psychiatric disorders, although there is no consensus about the specific risk alleles or haplotypes across studies.MethodsIn a case-control sample of German descent (affective psychosis: n = 248; controls: n = 188) we examined seven single nucleotide polymorphisms (SNPs) around DAOA/G30 (rs3916966, rs1935058, rs2391191, rs1935062, rs947267, rs3918342, and rs9558575) for genetic association in a polydiagnostic approach (ICD 10; Leonhard's classification).ResultsNo single marker showed evidence of overall association with affective disorder neither in ICD10 nor Leonhard's classification. Haplotype analysis revealed no association with recurrent unipolar depression or bipolar disorder according to ICD10, within Leonhard's classification manic-depression was associated with a 3-locus haplotype (rs2391191, rs1935062, and rs3916966; P = 0.022) and monopolar depression with a 5-locus combination at the DAOA/G30 core region (P = 0.036).ConclusionOur data revealed potential evidence for partially overlapping risk haplotypes at the DAOA/G30 locus in Leonhard's affective psychoses, but do not support a common genetic contribution of the DAOA/G30 gene complex to the pathogenesis of affective disorders.
Highlights
The DAOA/G30 (D-amino acid oxidase activator) gene complex at chromosomal region 13q32-33 is one of the most intriguing susceptibility loci for the major psychiatric disorders, there is no consensus about the specific risk alleles or haplotypes across studies
Association between bipolar affective disorder and the DAOA/G30 locus has first been reported in North American family-based samples at the intronic marker rs1935058, with significant association of the entire haplotype set [7]
Genetic evaluation of the core region of the DAOA/G30 gene complex was based on seven single nucleotide polymorphisms (SNPs) in a sample of 436 subjects (248 cases; Figure 1)
Summary
The DAOA/G30 (D-amino acid oxidase activator) gene complex at chromosomal region 13q32-33 is one of the most intriguing susceptibility loci for the major psychiatric disorders, there is no consensus about the specific risk alleles or haplotypes across studies. Association between bipolar affective disorder and the DAOA/G30 locus has first been reported in North American family-based samples at the intronic marker rs1935058, with significant association of the entire haplotype set [7]. In a more recent meta-analysis based on four case-control association studies none of five single markers (used in more than one study) showed evidence of overall association, but all SNPs showed significant evidence for heterogeneity between study designs and study samples [6,7,8,9,11]. In a comparison of “core syndromes” of bipolar disorder and schizophrenia, the DAOA/G30 locus showed overall association to lifetime episodes of disturbed emotions more than to psychosis itself [11]
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