| 1 | Am. J. Med. Genet. B Neuropsychiatr. Genet. 2005 Feb 133B: 1-5 |
|---|---|
| PMID | 15645418 |
| Title | Assessing the validity of blood-based gene expression profiles for the classification of schizophrenia and bipolar disorder: a preliminary report. |
| Abstract | Recent advances have facilitated the use of blood-derived RNA to conduct genomic analyses of human diseases. This emerging technology represents a rigorous and convenient alternative to traditional tissue biopsy-derived RNA, as it allows for larger sample sizes, better standardization of technical procedures, and the ability to non-invasively profile human subjects. In the present pilot study, we have collected RNA from blood of patients diagnosed with schizophrenia or bipolar disorder (BPD), as well as normal control subjects. Using microarray analysis, we found that each disease state exhibited a unique expressed genome signature, allowing us to discriminate between the schizophrenia, BPD, and control groups. In addition, we validated changes in several potential biomarker genes for schizophrenia and BPD by RT-PCR, and some of these were found to code to chromosomal loci previously linked to schizophrenia. Linear and non-linear combinations of eight putative biomarker genes (APOBEC3B, ADSS, ATM, CLC, CTBP1, DATF1, CXCL1, and S100A9) were able to discriminate between schizophrenia, BPD, and control samples, with an overall accuracy of 95%-97% as indicated by receiver operating characteristic (ROC) curve analysis. We therefore propose that blood cell-derived RNA may have significant value for performing diagnostic functions and identifying disease biomarkers in schizophrenia and BPD. |
| SCZ Keywords | schizophrenia, schizophrenics |
| 2 | BMC Med. Genet. 2008 -1 9: 119 |
| PMID | 19115993 |
| Title | Association analyses of the interaction between the ADSS and ATM genes with schizophrenia in a Chinese population. |
| Abstract | The blood-derived RNA levels of the adenylosuccinate synthase (ADSS) and ataxia telangiectasia mutated (ATM) genes were found to be down- and up-regulated, respectively, in schizophrenics compared with controls, and ADSS and ATM were among eight biomarker genes to discriminate schizophrenics from normal controls. ADSS catalyzes the first committed step of AMP synthesis, while ATM kinase serves as a key signal transducer in the DNA double-strand breaks response pathway. It remains unclear whether these changes result from mutations or polymorphisms in the two genes. Six SNPs in the ADSS gene and three SNPs in the ATM gene in a Chinese population of 488 schizophrenics and 516 controls were genotyped to examine their association with schizophrenia (SZ). Genotyping was performed using the Sequenom platform. There was no significant difference in the genotype, allele, or haplotype distributions of the nine SNPs between cases and controls. Using the Multifactor Dimensionality Reduction (MDR) method, we found that the interactions among rs3102460 in the ADSS gene and rs227061 and rs664143 in the ATM gene revealed a significant association with SZ. This model held a maximum testing accuracy of 60.4% and a maximum cross-validation consistency of 10 out of 10. These findings suggest that the combined effects of the polymorphisms in the ADSS and ATM genes may confer susceptibility to the development of SZ in a Chinese population. |
| SCZ Keywords | schizophrenia, schizophrenics |
| 3 | Behav Brain Funct 2008 -1 4: 39 |
| PMID | 18721483 |
| Title | An association study of ADSS gene polymorphisms with schizophrenia. |
| Abstract | Adenylosuccinate synthase (ADSS) catalyzes the first committed step of AMP synthesis. It was suggested that the blood-derived RNA of ADSS was down-regulated in schizophrenia (SZ) and one of the eight putative biomarker genes to discriminate SZ from normal controls. However, it remains unclear whether the reduction of ADSS RNA is due to the polymorphisms of the gene or not. We attempted to examine the association of ADSS gene with schizophrenia in a Chinese population of 480 schizophrenics and 502 normal controls. Genotyping was performed by the Sequenom platform. The 6 marker SNPs (rs3102460, rs3127459, rs3127460, rs3127465, rs3006001, and rs3003211) were genotyped. The frequencies of alleles, genotypes, and haplotypes were tested between cases and controls. There was no significant difference of genotypic, allelic, or haplotypic distributions of the 6 SNPs between the two groups. Our data did not support ADSS gene as a susceptibility gene for SZ in Chinese Han population. Large sample size study is needed to validate or replicate our association study, especially from other ethnic populations. |
| SCZ Keywords | schizophrenia, schizophrenics |
| 4 | BMC Med. Genet. 2008 -1 9: 119 |
| PMID | 19115993 |
| Title | Association analyses of the interaction between the ADSS and ATM genes with schizophrenia in a Chinese population. |
| Abstract | The blood-derived RNA levels of the adenylosuccinate synthase (ADSS) and ataxia telangiectasia mutated (ATM) genes were found to be down- and up-regulated, respectively, in schizophrenics compared with controls, and ADSS and ATM were among eight biomarker genes to discriminate schizophrenics from normal controls. ADSS catalyzes the first committed step of AMP synthesis, while ATM kinase serves as a key signal transducer in the DNA double-strand breaks response pathway. It remains unclear whether these changes result from mutations or polymorphisms in the two genes. Six SNPs in the ADSS gene and three SNPs in the ATM gene in a Chinese population of 488 schizophrenics and 516 controls were genotyped to examine their association with schizophrenia (SZ). Genotyping was performed using the Sequenom platform. There was no significant difference in the genotype, allele, or haplotype distributions of the nine SNPs between cases and controls. Using the Multifactor Dimensionality Reduction (MDR) method, we found that the interactions among rs3102460 in the ADSS gene and rs227061 and rs664143 in the ATM gene revealed a significant association with SZ. This model held a maximum testing accuracy of 60.4% and a maximum cross-validation consistency of 10 out of 10. These findings suggest that the combined effects of the polymorphisms in the ADSS and ATM genes may confer susceptibility to the development of SZ in a Chinese population. |
| SCZ Keywords | schizophrenia, schizophrenics |
| 5 | Behav Brain Funct 2008 -1 4: 39 |
| PMID | 18721483 |
| Title | An association study of ADSS gene polymorphisms with schizophrenia. |
| Abstract | Adenylosuccinate synthase (ADSS) catalyzes the first committed step of AMP synthesis. It was suggested that the blood-derived RNA of ADSS was down-regulated in schizophrenia (SZ) and one of the eight putative biomarker genes to discriminate SZ from normal controls. However, it remains unclear whether the reduction of ADSS RNA is due to the polymorphisms of the gene or not. We attempted to examine the association of ADSS gene with schizophrenia in a Chinese population of 480 schizophrenics and 502 normal controls. Genotyping was performed by the Sequenom platform. The 6 marker SNPs (rs3102460, rs3127459, rs3127460, rs3127465, rs3006001, and rs3003211) were genotyped. The frequencies of alleles, genotypes, and haplotypes were tested between cases and controls. There was no significant difference of genotypic, allelic, or haplotypic distributions of the 6 SNPs between the two groups. Our data did not support ADSS gene as a susceptibility gene for SZ in Chinese Han population. Large sample size study is needed to validate or replicate our association study, especially from other ethnic populations. |
| SCZ Keywords | schizophrenia, schizophrenics |