| 1 | Psychiatr. Genet. 2000 Sep 10: 139-43 |
|---|---|
| PMID | 11204350 |
| Title | A contribution to genome-wide association studies: search for susceptibility loci for schizophrenia using DNA microsatellite markers on chromosomes 19, 20, 21 and 22. |
| Abstract | As an initial step for genome-wide association studies, we sought an association between schizophrenia and 34 microsatellite markers on chromosomes 19, 20, 21 and 22 by a case-control design. The samples examined for an association were 168 schizophrenic patients and 146 control subjects in the Japanese population. The allele distribution of the 34 loci differed significantly between Japanese and French populations. Significant deviation from the Hardy-Weinberg equilibrium was observed at D19S209 and D21S1256 in the control subjects. Case-control comparisons of the initial screening revealed a significant difference in allele frequency at D20S95 and a trend of difference at D20S118. To confirm these possible associations, additional samples consisting of 110 schizophrenic patients and 116 control subjects were examined, and an association between D20S95 and schizophrenia was confirmed (corrected P value after Bonferroni correction, 0.00035). D20S95 is located close to the gene (CHGB) encoding chromogranin B. These findings suggest that CHGB could be an important candidate gene involved in the development of schizophrenia. |
| SCZ Keywords | schizophrenia, schizophrenic |
| 2 | Psychiatr. Genet. 2000 Sep 10: 139-43 |
| PMID | 11204350 |
| Title | A contribution to genome-wide association studies: search for susceptibility loci for schizophrenia using DNA microsatellite markers on chromosomes 19, 20, 21 and 22. |
| Abstract | As an initial step for genome-wide association studies, we sought an association between schizophrenia and 34 microsatellite markers on chromosomes 19, 20, 21 and 22 by a case-control design. The samples examined for an association were 168 schizophrenic patients and 146 control subjects in the Japanese population. The allele distribution of the 34 loci differed significantly between Japanese and French populations. Significant deviation from the Hardy-Weinberg equilibrium was observed at D19S209 and D21S1256 in the control subjects. Case-control comparisons of the initial screening revealed a significant difference in allele frequency at D20S95 and a trend of difference at D20S118. To confirm these possible associations, additional samples consisting of 110 schizophrenic patients and 116 control subjects were examined, and an association between D20S95 and schizophrenia was confirmed (corrected P value after Bonferroni correction, 0.00035). D20S95 is located close to the gene (CHGB) encoding chromogranin B. These findings suggest that CHGB could be an important candidate gene involved in the development of schizophrenia. |
| SCZ Keywords | schizophrenia, schizophrenic |
| 3 | Biol. Psychiatry 2004 Jul 56: 10-7 |
| PMID | 15219467 |
| Title | Association between chromogranin b gene polymorphisms and schizophrenia in the Japanese population. |
| Abstract | We found in previous work a significant association between schizophrenia and D20S95 on chromosome 20p12.3. In this study, we analyzed 10 microsatellite markers and found an association of schizophrenia with D20S882 and D20S905 that flank D20S95. The chromogranin B gene (CHGB) is 30 kb from D20S905. The chromogranin B (secretogranin I) belongs to a series of acidic secretory proteins that are widely expressed in endocrine and neuronal cells, and its cerebrospinal fluid levels have been reported to decrease in patients with chronic schizophrenia. We screened for polymorphisms in CHGB with polymerase chain reaction direct sequencing methods in 24 Japanese schizophrenic patients and identified a total of 22 polymorphisms. Allelic and genotypic distributions of detected polymorphisms were compared between unrelated Japanese schizophrenic patients (n = 192) and healthy control subjects (n = 192). Statistically significant differences in the allelic distributions were found between schizophrenic patients and control subjects for 1058C/G (A353G) (corrected p = 7.7 x 10(-5)) and 1104A/G (E368E) (corrected p = 8.1 x 10(-6)). The 1058C/G and 1104A/G alleles were in almost complete linkage disequilibrium and were in linkage disequilibrium with D20S95. Results suggest that the CHGB variations are involved in the susceptibility to schizophrenia in our study population. |
| SCZ Keywords | schizophrenia, schizophrenic |
| 4 | Biol. Psychiatry 2004 Jul 56: 10-7 |
| PMID | 15219467 |
| Title | Association between chromogranin b gene polymorphisms and schizophrenia in the Japanese population. |
| Abstract | We found in previous work a significant association between schizophrenia and D20S95 on chromosome 20p12.3. In this study, we analyzed 10 microsatellite markers and found an association of schizophrenia with D20S882 and D20S905 that flank D20S95. The chromogranin B gene (CHGB) is 30 kb from D20S905. The chromogranin B (secretogranin I) belongs to a series of acidic secretory proteins that are widely expressed in endocrine and neuronal cells, and its cerebrospinal fluid levels have been reported to decrease in patients with chronic schizophrenia. We screened for polymorphisms in CHGB with polymerase chain reaction direct sequencing methods in 24 Japanese schizophrenic patients and identified a total of 22 polymorphisms. Allelic and genotypic distributions of detected polymorphisms were compared between unrelated Japanese schizophrenic patients (n = 192) and healthy control subjects (n = 192). Statistically significant differences in the allelic distributions were found between schizophrenic patients and control subjects for 1058C/G (A353G) (corrected p = 7.7 x 10(-5)) and 1104A/G (E368E) (corrected p = 8.1 x 10(-6)). The 1058C/G and 1104A/G alleles were in almost complete linkage disequilibrium and were in linkage disequilibrium with D20S95. Results suggest that the CHGB variations are involved in the susceptibility to schizophrenia in our study population. |
| SCZ Keywords | schizophrenia, schizophrenic |
| 5 | Hum. Mutat. 2004 Jan 23: 1-7 |
| PMID | 14695526 |
| Title | VSD: a database for schizophrenia candidate genes focusing on variations. |
| Abstract | schizophrenia is a common mental disease characterized by delusions, hallucinations, and formal thought disorder. It has been demonstrated with genetic evidence that the disease is a polygenic disorder. Pharmacological, neurochemical, and clinical studies have suggested a number of schizophrenia susceptibility loci. In order to systematically search for genes with small effect in the development of schizophrenia, a database called VSD was established to provide variation data for publicly available candidate genes. Most of the genes encode neurotransmitter receptors, neurotransmitter transporters, and the enzymes involved in their metabolism. Other candidate genes extracted from published literature are also included. The variation information has been collected from publicly available mutation and polymorphism databases such as dbSNP, HGVbase, and OMIM, with single nucleotide polymorphism (SNP) being the most abundant form of collected variations. Reference sequences from NCBI's RefSeq database are used as references when positioning variation at transcript and protein levels. The nonsynonymous SNPs (nsSNPs) that lead to amino acid changes in the functional sites or domains of proteins are distinguished since they are more likely to affect protein function and would be target SNPs for association studies. In addition to variation data, gene descriptions, enzyme information, and other biological information for each gene locus are also included. The latest version of VSD contains 23,648 variations assigned to a total of 186 genes. Five-hundred eighty-eight domains and sites annotated in the SWISS-PROT and InterPro databases are found to contain nsSNPs. VSD may be accessed via the World Wide Web (www.CHGB.org.cn/vsd.htm) and will be developed as an up-to-date and comprehensive locus-specific resource for identifying susceptibility genes for schizophrenia. |
| SCZ Keywords | schizophrenia, schizophrenic |
| 6 | J Neural Transm (Vienna) 2007 -1 114: 641-4 |
| PMID | 17143778 |
| Title | Further evidence that the chromogranin B gene confers predisposition to schizophrenia: a family-based association study in Chinese. |
| Abstract | The Chromogranin B (CHGB) gene has been proposed as a candidate gene for predisposition to schizophrenia due to its location on the genome, the evidence of genetic studies, and its functional role in schizophrenia. To investigate its association with schizophrenia using case-control analysis, we genotyped eight single nucleotide polymorphisms (SNPs) and performed transmission disequilibrium tests (TDT) using 192 Han Chinese trios. The G allele of IVS4 + 808A > G showed a trend of over-transmission from heterozygous parents to affected offspring (P = 0.06), although no significant over-transmission was found for individual markers. Furthermore, a significant transmission was observed for the common haplotype G-G-A-G-C (P = 0.0018). Overall, our results suggest that at least one locus in or close to the CHGB gene confers risk of the disorder and strengthen the evidence that CHGB is a promising susceptibility gene for schizophrenia in Chinese population. |
| SCZ Keywords | schizophrenia, schizophrenic |
| 7 | J. Hum. Genet. 2010 May 55: 285-92 |
| PMID | 20339380 |
| Title | An integrated genomic analysis of gene-function correlation on schizophrenia susceptibility genes. |
| Abstract | schizophrenia is a highly complex inheritable disease characterized by numerous genetic susceptibility elements, each contributing a modest increase in risk for the disease. Although numerous linkage or association studies have identified a large set of schizophrenia-associated loci, many are controversial. In addition, only a small portion of these loci overlaps with the large cumulative pool of genes that have shown changes of expression in schizophrenia. Here, we applied a genomic gene-function approach to identify susceptibility loci that show direct effect on gene expression, leading to functional abnormalities in schizophrenia. We carried out an integrated analysis by cross-examination of the literature-based susceptibility loci with the schizophrenia-associated expression gene list obtained from our previous microarray study (Journal of Human Genetics (2009) 54: 665-75) using bioinformatic tools, followed by confirmation of gene expression changes using qPCR. We found nine genes (CHGB, SLC18A2, SLC25A27, ESD, C4A/C4B, TCP1, CHL1 and CTNNA2) demonstrate gene-function correlation involving: synapse and neurotransmission; energy metabolism and defense mechanisms; and molecular chaperone and cytoskeleton. Our findings further support the roles of these genes in genetic influence and functional consequences on the development of schizophrenia. It is interesting to note that four of the nine genes are located on chromosome 6, suggesting a special chromosomal vulnerability in schizophrenia. |
| SCZ Keywords | schizophrenia, schizophrenic |