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- Title
Comprehensive analysis of polymorphisms throughout GAD1 gene: a family-based association study in schizophrenia.
- Authors
Du, J.; Duan, S.; Wang, H.; Chen, W.; Zhao, X.; Zhang, A.; Wang, L.; Xuan, J.; Yu, L.; Wu, S.; Tang, W.; Li, X.; Li, H.; Feng, G.; Xing, Q.; He, L.
- Abstract
Studies suggest that GAD1 gene is a functional candidate susceptibility gene for schizophrenia. In order to investigate the contribution of GAD1 gene to the etiology of schizophrenia in Chinese, we carried out a family-based association study between GAD1 gene and schizophrenia in 235 Chinese Han family trios. The GAD1 gene is comprehensively analyzed using a systematic mutation scan and the following-up association studies between common SNPs and schizophrenia in both single-locus and haplotype levels. Altogether, we have found 17 variants including 10 SNPs in 5′-flanking regions, 4 SNPs and one novel in-del in intronic regions and 2 SNPs (one novel SNP) in the 3′-untranslated region (UTR). Using the transmission disequilibrium test of the 9 common SNPs out of 17 variants, Significant evidence of SNP rs3791878-G allele in 5′-flanking region of GAD1 was preferentially transmitted to both the all offsprings of the trios ( P = 0.0063, respectively; odds ratio = 1.83; 95% confidence interval: 1.26–2.65) and the male offsprings the trios ( P = 0.0045, respectively; odds ratio = 2.21; 95% confidence interval: 1.37–3.56). Haplotype analysis suggested that rs3762556(C)–rs3791878(G)–rs6755102(C) is the major risky haplotype preferentially transmitted in both all the trios and male-offspring trios (Global P = 0.016 and 0.012, respectively). The gender-dependent of the risk of SNP rs3791878 suggest the complexity of GAD1 gene in schizophrenia. Given that the switch from G to T in SNP rs3791878 might cause the loss of ARNT and XBP1 transcriptional factor binding sites using a bioinformatics approach, our positive findings of this SNP support the hypothesis that the abruption of GAD1 gene is important to the risk of schizophrenia.
- Subjects
GENETIC polymorphisms; SCHIZOPHRENIA; GLUTAMATE decarboxylase; PSYCHOSES; DECARBOXYLASES; CHINESE people
- Publication
Journal of Neural Transmission, 2008, Vol 115, Issue 3, p513
- ISSN
0300-9564
- Publication type
Article
- DOI
10.1007/s00702-007-0844-z