ZNF804A and schizophrenia susceptibility in Asian populations.

ZNF804A, a recently identified risk gene for schizophrenia, has been extensively investigated and the principle finding for this locus has been the association with SNP rs1344706 in populations of European ancestries. However, in Asian populations, only a few studies have been conducted for rs1344706 and the results were inconsistent. Here, we studied rs1344706 and schizophrenia susceptibility in multiple Asian case-control samples (10 Chinese and 2 Japanese samples; N = 21,062), and the meta-analyses indicated non-significant association of rs1344706 with schizophrenia (P = 0.26), suggesting the same SNP identified in European samples is not predisposing risk in Asians. Further genotyping and association analyses of a set of SNPs spanning the entire genomic region of ZNF804A (520 kb) identified no association except for SNP rs359895 (P = 7.8 x 10(-5) , N = 5,172), a newly reported risk SNP located in the ZNF804A promoter region with functional implications. This suggests that ZNF804A may also contribute to schizophrenia susceptibility in Asians although the risk SNP is different from that in Europeans, and it was supported by the detected up-regulation of ZNF804A mRNA expression in the blood cells of Chinese schizophrenia patients compared with normal controls (P = 0.004). Additionally, the linkage disequilibrium (LD) structure analyses using data from HapMap indicated distinct LD blocks across ZNF804A between Chinese and Europeans, which may explain the different association patterns between them, and also highlight the compounding difficulty of genetic studies of complex diseases like schizophrenia when studying multiple ethnic populations.

The functional polymorphisms linked with interleukin-1ß gene expression are associated with bipolar disorder.

BACKGROUND: Bipolar disorder (BD) is a severe psychiatric illness attributable to multifactorial risk components (e.g. environmental stimuli, neuroinflammation, etc.), and genetic variations affecting these risk components are considered pivotal predisposing factors. The interleukin-1ß (IL-1ß) gene and its protein product have been repeatedly highlighted in the pathogenesis of BD. As functional polymorphisms and haplotypes linked with IL-1ß mRNA expression have been reported, whether they are correlated with the risk of developing BD remains to be tested. METHODS: To examine whether variations in the IL-1ß gene locus confer genetic risk of BD, we recruited 930 BD patients and 912 healthy controls for the current study. All subjects were Han Chinese, and were age- and gender-matched. We tested seven functional single nucleotide polymorphisms (SNPs) spanning the IL-1ß gene and one haplotype composed of three SNPs for their associations with risk of BD. RESULTS: We found that the functional SNPs in the promoter region of IL-1ß gene were significantly associated with risk of BD. The haplotype analyses further supported the involvement of IL-1ß promoter SNPs in BD. The BD risk SNPs in our study have been previously reported to predict higher IL-1ß levels in the brain and peripheral blood, which is consistent with the clinical observation of elevated IL-1ß levels in the lymphocytes or peripheral blood of patients with BD compared with healthy subjects. CONCLUSION: Our results support the contention that IL-1ß is likely a risk gene for BD, and further investigations on this gene may promote our understanding and clinical management of this illness.

No evidence of an association between MIR137 rs1625579 and schizophrenia in Asians: a meta-analysis in 30 843 individuals.

INTRODUCTION: Schizophrenia is a severe neuropsychiatric disorder with high heritability. A single nucleotide polymorphism rs1625579 in the miR-137 gene has recently been reported to confer risk of schizophrenia by a genome-wide association study in populations of European ancestry. However, subsequent association studies in Asian populations yielded inconsistent results. MATERIALS AND METHODS: To carry out a systematic meta-analysis of rs1625579 with schizophrenia in Asian populations, we collected phenotypic and genetic data from individual replication samples of up to 11 887 schizophrenic patients, 16 660 normal controls, and 579 families. RESULTS: The results from analysis after pooling all the eligible case-control and family-based samples suggest that rs1625579 was not associated with schizophrenia in Asian populations (P=0.161, odds ratio=1.074). Moderate genetic heterogeneity was found between individual samples (P=0.130, I=34.7%). 'Leave-one-out' sensitivity analysis showed that removal of any of the individual samples did not lead to significant associations. CONCLUSION: We could not confirm the significant association of rs1625579 with schizophrenia in Asian samples, which may have resulted from potential genetic heterogeneity on this locus between continental populations.

Further evidence of VRK2 rs2312147 associated with schizophrenia.

OBJECTIVES: Previous genome-wide association studies (GWAS) have reported that rs2312147 near the VRK2 gene was significantly associated with schizophrenia in populations of European descent, but negative results have also been observed. METHODS: To perform a systematic meta-analysis, we collected statistical data of rs2312147 from both GWAS and individual replication samples in European and Asian populations, which finally included up to 30,867 schizophrenia patients and 59,863 healthy controls. RESULTS: The VRK2 rs2312147 was genome-wide significantly associated with schizophrenia in combined populations (P = 1.31 × 10(-15), odds ratio, OR = 1.10) as well as in Europeans only (P = 2.35 × 10(-12), OR =1.09). In Asian samples, the SNP did not reach genome-wide level of statistical significance (P = 1.23 × 10 (-) (5), OR =1.19), which is likely due to the limited power of small sample size in this population (2,974 cases and 4,786 controls). However, the effect size of rs2312147 did not alter significantly between populations, and is also in agreement with the observed effect sizes of other genetic risk loci in large scale studies. CONCLUSIONS: Our data provides further evidence for the genetic contributions of VRK2 rs2312147 to schizophrenia susceptibility especially in Europeans, while further replication analyses in Asian populations are still needed, and future studies, e.g., the underlying molecular mechanisms of genetic risk, are necessary.

Analysis of common genetic variants identifies RELN as a risk gene for schizophrenia in Chinese population.

UNLABELLED: Abstract Objectives. Several lines of evidence have shown that both RELN mRNA and protein are possibly down-regulated in the brain of schizophrenia patients. Recent association studies in European populations suggested RELN as a risk gene for schizophrenia. In this study, we test if RELN contributes to the risk of schizophrenia in Chinese population. Methods. We conducted case-control association analysis of 19 representative single nucleotide polymorphisms (SNPs) spanning the entire region of RELN in two independent Han Chinese samples from southwestern China (the Kunming sample and the Yuxi sample). Results. We identified six SNPs significantly associated with schizophrenia in the Kunming sample and four of them remained significant in the combined samples (the P values range from 0.006 to 4.0 × 10(-5)). Haplotype analysis also suggested significant associations for the haplotypes incorporating the six significant SNPs (global P < 1.0 × 10(-5)). Additionally, we also observed several other haplotypes (defined by a different set of SNPs) significantly associated with schizophrenia in the Kunming sample. However, the reported association of rs7341475 in Ashkenazi Jews was not significant in Han Chinese. CONCLUSIONS: Our findings demonstrate that RELN is a susceptibility gene for schizophrenia in Chinese population, and it is likely a common risk gene for schizophrenia in major populations worldwide.

Association of RELN promoter SNPs with schizophrenia in the Chinese population.

Previous research on gene expression analysis and association tests have suggested that RELN is a risk gene for schizophrenia in world populations. Based on the reported down-regulation of RELN in schizophrenia patients compared with normal subjects, we speculated that variants in the RELN promoter region may confer risk for schizophrenia. In this study, we investigated the associations of three SNPs in the promoter region of RELN with schizophrenia in a case-control sample from southwestern China (940 cases and 1 369 controls). The results suggested that none of the SNPs showed significant associations in our sample, indicating the risk variants for schizophrenia in RELN may not be located in the promoter region. We also performed meta-analysis by combining our data with previously reported data on the Chinese population with a total sample size of 2 843 individuals, and the result remained non-significant. Collectively, our results suggested variants in the RELN promoter may not harbor risk SNPs associated with schizophrenia in the Chinese population.