| 1 | Mol. Psychiatry 2011 Nov 16: 1117-29 |
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| PMID | 20838396 |
| Title | GWA study data mining and independent replication identify cardiomyopathy-associated 5 (CMYA5) as a risk gene for schizophrenia. |
| Abstract | We conducted data-mining analyses using the Clinical Antipsychotic Trials of Intervention Effectiveness (CATIE) and molecular genetics of schizophrenia genome-wide association study supported by the genetic association information network (MGS-GAIN) schizophrenia data sets and performed bioinformatic prioritization for all the markers with P-values ?0.05 in both data sets. In this process, we found that in the CMYA5 gene, there were two non-synonymous markers, rs3828611 and rs10043986, showing nominal significance in both the CATIE and MGS-GAIN samples. In a combined analysis of both the CATIE and MGS-GAIN samples, rs4704591 was identified as the most significant marker in the gene. Linkage disequilibrium analyses indicated that these markers were in low LD (3?828?611-rs10043986, r(2)=0.008; rs10043986-rs4704591, r(2)=0.204). In addition, CMYA5 was reported to be physically interacting with the DTNBP1 gene, a promising candidate for schizophrenia, suggesting that CMYA5 may be involved in the same biological pathway and process. On the basis of this information, we performed replication studies for these three single-nucleotide polymorphisms. The rs3828611 was found to have conflicting results in our Irish samples and was dropped out without further investigation. The other two markers were verified in 23 other independent data sets. In a meta-analysis of all 23 replication samples (family samples, 912 families with 4160 subjects; case-control samples, 11?380 cases and 15?021 controls), we found that both markers are significantly associated with schizophrenia (rs10043986, odds ratio (OR)=1.11, 95% confidence interval (CI)=1.04-1.18, P=8.2 × 10(-4) and rs4704591, OR=1.07, 95% CI=1.03-1.11, P=3.0 × 10(-4)). The results were also significant for the 22 Caucasian replication samples (rs10043986, OR=1.11, 95% CI=1.03-1.17, P=0.0026 and rs4704591, OR=1.07, 95% CI=1.02-1.11, P=0.0015). Furthermore, haplotype conditioned analyses indicated that the association signals observed at these two markers are independent. On the basis of these results, we concluded that CMYA5 is associated with schizophrenia and further investigation of the gene is warranted. |
| SCZ Keywords | schizophrenia |
| 2 | Schizophr. Res. 2011 Jul 129: 217-9 |
| PMID | 21295948 |
| Title | A common variant of the cardiomyopathy associated 5 gene (CMYA5) is associated with schizophrenia in Chinese population. |
| Abstract | -1 |
| SCZ Keywords | schizophrenia |
| 3 | Prog. Neuropsychopharmacol. Biol. Psychiatry 2013 Oct 46: 64-9 |
| PMID | 23778016 |
| Title | Genetic analysis of common variants in the CMYA5 (cardiomyopathy-associated 5) gene with schizophrenia. |
| Abstract | Recently, CMYA5 was suggested as a susceptibility gene for schizophrenia based on two independent studies utilizing different ethnic samples. We designed a case-control study to examine whether 21 SNPs contained within CMYA5 were associated with the disorder in a western Han Chinese sample comprised of 488 schizophrenia patients and 516 healthy control subjects. The allele distribution of SNPs rs7714250, rs16877135 and rs13158477 showed significant association with schizophrenia (Puncorrected=0.008, Puncorrected=0.04, and Puncorrected=0.009, respectively) as well as the genotype distribution in the Cochran-Armitage trend test (Puncorrected=0.008, Puncorrected=0.037 and Puncorrected=0.011, respectively). After Bonferroni correction, rs7714250 showed a trend of association with schizophrenia both in allele distribution (Pcorrected=0.088) and genotype distribution (Pcorrected=0.088). Furthermore, significant associations were found in several two-, three-, four-, and five-SNP tests of haplotype analyses. Replications of the association of CMYA5 with schizophrenia across various studies suggest that it is very likely a potential common schizophrenia-related gene worldwide. Functional studies correlating CMYA5 with DTNBP1 and PKA warrant further investigation of the molecular basis of this gene in relationship to the signal transduction pathway(s) underlying the pathogenesis of schizophrenia. |
| SCZ Keywords | schizophrenia |
| 4 | Psychiatr. Genet. 2013 Aug 23: 179-80 |
| PMID | 23528614 |
| Title | An association analysis of the cardiomyopathy-associated 5 (CMYA5) gene with schizophrenia in a Japanese population. |
| Abstract | -1 |
| SCZ Keywords | schizophrenia |
| 5 | World J. Biol. Psychiatry 2014 Sep 15: 553-60 |
| PMID | 24988482 |
| Title | The CMYA5 gene confers risk for both schizophrenia and major depressive disorder in the Han Chinese population. |
| Abstract | A recent genome-wide association study (GWAS) of the European population implicated the CMYA5 gene in schizophrenia. Previous functional studies showed that the CMYA5 protein can interact with DTNBP1 and PKA, providing further support for a role of CMYA5 in the pathogenesis of schizophrenia. However, this association requires additional validation in independent populations. To validate the association between CMYA5 and schizophrenia and major depressive disorder, we genotyped 16 SNPs within the CMYA5 gene and performed case-control studies in 1330 schizophrenia patients, 1045 patients with major depressive disorder, and 1235 normal controls. All patients were of Han Chinese origin. rs6883197 and rs259127 were significantly associated with schizophrenia, and rs12514461, rs259127, and rs7343 were associated with major depressive disorder. Additionally, one risk haplotype of rs16877109-rs3828611 (G-G) was associated with both schizophrenia (P = 0.0000784, after correction) and major depressive disorder (P = 0.00230, after correction). Our findings support the idea that specific alleles and haplotype in the CMYA5 confer genetic risk for both schizophrenia and major depressive disorder in the Han Chinese population. |
| SCZ Keywords | schizophrenia |
| 6 | Asian J Psychiatr 2014 Feb 7: 95-6 |
| PMID | 24524722 |
| Title | The cardiomyopathy-associated 5 (CMYA5) gene and risk of schizophrenia: meta-analysis of rs3828611 and rs4704591 in East Asian populations. |
| Abstract | -1 |
| SCZ Keywords | schizophrenia |
| 7 | Early Interv Psychiatry 2015 Sep -1: -1 |
| PMID | 26403435 |
| Title | Association between CMYA5 gene polymorphisms and risk of schizophrenia in Uygur population and a meta-analysis. |
| Abstract | Previous evidence has found that some single nucleotide polymorphisms (SNPs) in cardiomyopathy-associated 5 gene (CMYA5) were associated with schizophrenia in the Caucasian and Chinese Han populations. In this study, we aimed to investigate the relationship between CMYA5 gene polymorphisms and schizophrenia in Chinese Uygur population and perform a meta-analysis to synthetically analyse the association of CMYA5 gene polymorphisms with schizophrenia in Asian populations. We retrospectively analysed 985 schizophrenia cases and 1123 healthy controls in Chinese Uygur population. Four SNPs (rs259127, rs3828611, rs4704591 and rs6883197) of CMYA5 were genotyped using TaqMan SNP genotyping assay. Meta-analysis was conducted across Asian studies by Review Manager 5.2. Results showed no significant difference in either allelic or genotypic frequency in four SNPs of the CMYA5 gene between cases and controls (P?>?0.05). However, the age of onset and the PANSS positive-factor subscale score were significantly lower in schizophrenia patients with the A/A genotype of rs6883197 than those with A/G and G/G genotypes (P?schizophrenia (P?=?0.03, OR?=?0.92, 95% CI: 0.91-0.99). Our results support the association between CMYA5?rs6883197 and schizophrenia in Chinese Uygur population. Meta-analysis demonstrated that rs3828611 was significantly associated with schizophrenia in Asian population. Genetic heterogeneity among populations may be the main reason of results conflict between studies. In conclusion, association between CMYA5 gene polymorphisms and schizophrenia was confirmed in Asian population. |
| SCZ Keywords | schizophrenia |