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Allelic association of G72/G30 with schizophrenia and bipolar disorder: a comprehensive meta-analysis.

ABSTRACT: The G72/G30 gene complex (G72 also known as D-amino acid oxidase activator, DAOA) and its chromosomal region 13q32-34 have been linked and associated with both schizophrenia (SCZ) and bipolar disorder (BP) in multiple studies, including our initial association report on BP. However, the inconsistency of associated variants across studies is obvious. Previous meta-analyses had small data sets. The present meta-analysis combined 18 association articles published before April of 2007. There were 19 independent studies of SCZ, with 4304 cases, 5423 controls, and 1384 families, and four independent studies of BP with 1145 cases, 1829 controls, and 174 families. Of 15 single nucleotide polymorphisms (SNPs) analyzed in the 95-kb G72/G30 gene region, M18/rs947267 and M22/rs778293 showed association with SCZ in Asians, and M24/rs1421292 with SCZ in Europeans. The associations of C allele at M18 and A allele at M22 with SCZ in Asians survived conservative Bonferroni correction for multiple testing for 15 markers and subgroup analysis (adjusted P=0.0000253 for M18; adjusted P=0.009 for M22). No single maker showed evidence of overall association with BP. These results suggest that G72/G30 may influence susceptibility to schizophrenia with weak effects.

SUBMITTER: Shi J

PROVIDER: S-EPMC2237895 | biostudies-literature | 2008 Jan

REPOSITORIES: biostudies-literature

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Allelic association of G72/G30 with schizophrenia and bipolar disorder: a comprehensive meta-analysis.

Shi Jiajun J Badner Judith A JA Gershon Elliot S ES Liu Chunyu C

Schizophrenia research 20071126 1-3

The G72/G30 gene complex (G72 also known as D-amino acid oxidase activator, DAOA) and its chromosomal region 13q32-34 have been linked and associated with both schizophrenia (SCZ) and bipolar disorder (BP) in multiple studies, including our initial association report on BP. However, the inconsistency of associated variants across studies is obvious. Previous meta-analyses had small data sets. The present meta-analysis combined 18 association articles published before April of 2007. There were 19 ...[more]

PMID: 18023149

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Project description:A novel susceptibility locus (rs11098403) for schizophrenia and bipolar disorder (BD) was identified in an Ashkenazi Jewish population by a recent large-scale genome-wide association study. The rs11098403 is located in the vicinity of the gene encoding N-deacetylase/N-sulfotransferase (heparan glucosaminyl) 3, (NDST3). This study aimed to replicate the results in a Han Chinese population and then potentially extend these findings. We performed a two-stage study to investigate the association of NDST3 with the schizophrenia and BD risk in the Han Chinese. In stage 1, a total of 632 patients with schizophrenia, 654 patients with BD and 684 healthy controls were recruited from the Shanghai region. In stage 2, 522 schizophrenia patients and 547 normal subjects were enrolled from the Hangzhou region. Then, we conducted a meta-analysis based on the present literature. In stage 1, the single nucleotide polymorphism (SNP) rs11098403 showed a significant association with schizophrenia (corrected P=0.005). The frequency of the rs11098403 G allele was significantly lower among schizophrenia patients than among the controls (odds ratio (OR)=0.68, 95% confidence interval (CI): 0.55-0.84, corrected P=0.002). No significant difference was observed in individual SNP marker genotypes or allele distributions between the BD and control groups. In stage 2, the association of rs11098403 with schizophrenia could be validated (genotypic P=0.001 and allelic P=0.0003). After pooling all data from 1861 patients with schizophrenia and 2081 controls, we observed a significant association of the rs11098403 G allele with schizophrenia (Z=5.56, P<0.001), with an OR=0.70 (95% CI: 0.61-0.79). Then, we performed an expression quantitative trait loci analysis to investigate the functional effect of rs11098403 on NDST3 expression in the brain. We observed a significant association of rs11098403 with NDST3 expression in the hippocampus (P=0.027), although the significance did not survive after multiple testing correction. Our findings provided preliminary evidence that rs11098403 might modify the genetic risk of schizophrenia in the Han Chinese. Further investigations are warranted to identify the precise mechanism regulating brain NDST3 expression in the Han Chinese. These results would help to explain the pathophysiological mechanism of schizophrenia.

Dataset Information

Allelic association of G72/G30 with schizophrenia and bipolar disorder: a comprehensive meta-analysis.

Publications

Allelic association of G72/G30 with schizophrenia and bipolar disorder: a comprehensive meta-analysis.

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