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Background At present, the schizophrenia diagnoses are based on the clinical symptoms and behaviors neglecting the laboratory test indicators. Results To better investigate the diagnostic potential of miRNAs for schizophrenia, we selected 14 candidate miRNAs and examined their expressions in the serums of 40 schizophrenia patients and 40 healthy controls by qRT-PCR. Ultimately three abnormally expressed microRNAs were identified, i.e., miR-34a-5p, miR-432-5p and miR-449a. Then, binary regression analysis was employed to combine 3 dysregulated miRNAs. ROC analysis revealed that the AUC of the combination of miR-432-5p + miR-449a in serums was 0.841 (95% CI: 0.791~0.887) with 90% sensitivity and 80% specificity. The AUC of the combination of miR-34a-5p + miR-432-5p + miR-449a in serums was 0.843 (95% CI: 0.791~0.887) with 90% sensitivity and 77.5% specificity. The results indicated that the combined model of miR-432-5p + miR-449a and miR-34a-5p + miR-432-5p + miR-449a have better prediction performances. Conclusions The study concludes that the two miRNAs combinations have the potential to be used as biomarkers for schizophrenia diagnoses. The finding may be conducive to overcoming the dilemmas faced by current schizophrenia diagnosis.

Aim/objectives/background ZNF804A has been investigated widely as a candidate susceptibility gene for mental disorders in individuals of different ethnicities. However, in the Han Chinese population, most studies of this gene have focused on associations of the common single nucleotide polymorphism (SNP) rs1344706. Methods To investigate additional common variants within ZNF804A, we carried out a case-control study of 13 SNPs distributed across the whole gene, in 1330 schizophrenic patients, 1045 major depressive disorder patients, and 1235 normal controls. Results and conclusions We found that rs12476147 (P=0.0078) was associated significantly with schizophrenia, but no SNPs showed statistically significant associations with major depressive disorder after Bonferroni correction. Moreover, we also found that haplotype block 2, which included rs12476147 and rs1344706, was associated significantly with schizophrenia and major depressive disorder. Nevertheless, we could not replicate the association of rs1344706 with schizophrenia. In conclusion, the common variant rs12476147 and the related haplotype block in ZNF804A were associated significantly with schizophrenia in the Han Chinese population.

Objectives: The ATP-binding cassette transporter superfamily is one of the largest membrane protein families, which is responsible for transportation of substances across the membranes by utilising energy. Some research has bridged the variations in ABCA13 with occurrence of psychiatric disorders. To investigate the overlapping risk conferred by ABCA13 for both major depressive disorder and schizophrenia, we analysed tag single nucleotide polymorphisms (tag SNPs).Methods: We used TaqMan® technology to genotype 1045 major depressive disorder patients, 1235 schizophrenia patients and 1235 healthy controls of Han Chinese origin.Results: We found that rs7789493 (Pallele = 7.23E-04, Pgenotype =.001) was associated with major depressive disorder, while rs17132388 (Pallele = 1.63E-04, Pgenotype = 7.50E-04) and rs6583476 (Pallele = 5.50E-04, Pgenotype =.002) showed statistically significant association with schizophrenia.Conclusions: Our results indicate that the ABCA13 gene may contain overlapping common...

NVL (nuclear VCP (valosin containing protein)/p97-Like), a member of the AAA-ATPase (ATPases associated with various cellular activities) family, encodes a novel hTERT (human telomerase reverse transcriptase)-interacting protein NVL2 which is a telomerase component essential for holoenzyme assembly. Previous researches have reported the impacts of telomerase activity on mental illness and the potential association between NVL and major depressive disorder. To validate the susceptibility of NVL to major depressive disorder, and to investigate the overlapping risk conferred by NVL for both major depressive disorder and schizophrenia, we analyzed 9 tag single nucleotide polymorphisms (tag SNPs) using TaqMan® technology, in 1045 major depressive disorder patients, 1235 schizophrenia patients and 1235 normal controls of Han Chinese origin. We found that rs10916583 (Pallele = 0.020, Pgenotype = 0.028, OR = 1.156) and rs16846649 (adjusted Pallele = 0.014, Pgenotype = 0.007, OR = 0.718) were associated with major depressive disorder, while rs10916583 (adjusted Pallele = 1.08E − 02, OR = 1.213), rs16846649 (adjusted Pallele = 7.40E − 06, adjusted Pgenotype = 8.07E − 05, OR = 0.598) and rs10799541 (adjusted Pallele = 8.10E − 03, adjusted Pgenotype = 0.049, OR = 0.826) showed statistically significant association with schizophrenia after Bonferroni correction. Furthermore, rs10916583 (adjusted Pallele = 9.00E − 03, adjusted Pgenotype = 3.15E − 02, OR = 1.187) and rs16846649 (adjusted Pallele = 8.92E − 06, adjusted Pgenotype = 8.84E − 05, OR = 0.653) remained strongly associated with the analysis of combined cases of major depressive disorder and schizophrenia after Bonferroni correction. Our results indicated that the NVL gene may contain overlapping common genetic risk factors for major depressive disorder and schizophrenia in the Han Chinese population. The roles of NVL in telomerase biogenesis were also highlighted in psychiatric pathogenesis. The study on variants conferring overlapping risk for multiple psychiatric disorders could be tangible pathogenesis support and clinical or diagnostic references.

Background: Glycogen synthease kinase-3B is a key gene encoding a protein kinase which is abundant in brain, and is involved in signal transduction cascades of neuronal cell development and energy metabolism. Previous researches proposed GSK3B as a potential region for schizophrenia. Method: To validate the susceptibility of GSK3B to major depressive disorder, and to investigate the overlapping risk conferred by GSK3B for mental disorders, we performed a large-scale case-control study, analyzed 6 tag single nucleotide polymorphisms using TaqMan® technology in 1,045 major depressive disorder patients, 1,235 schizophrenia patients and 1,235 normal controls of Han Chinese origin. Results: We found rs334535 ( P allele =2.79E−03, P genotype =5.00E−03, OR=1.429) and rs2199503 ( P allele =0.020, P genotype = 0.040, OR=1.157) showed association with major depressive disorder before Bonferroni correction. rs6771023 (adjusted P allele =1.64E−03, adjusted P genotype =6.00E−03, OR=0.701) and rs2199503 (adjusted P allele =0.001, adjusted P genotype =0.002, OR=1.251) showed significant association with schizophrenia after Bonferroni correction. rs2199503 (adjusted P allele =1.70E−03, adjusted P genotype =0.006, OR=1.208) remained to be significant in the combined cases of major depressive disorder and schizophrenia after Bonferroni correction. Limitations: Further validations of our findings in samples with larger scale are suggested, and functional genomic study is needed to elucidate the role of GSK3B in signal pathway and psychiatric disorders. Conclusions: Our results provide evidence that the GSK3B gene could be a promising region which contains genetic risk for both major depressive disorder and schizophrenia in the Han Chinese population. The study on variants conferring overlapping risk for multiple psychiatric disorders could be tangible pathogenesis support and clinical or diagnostic references.

Schizophrenia (SCZ) and major depressive disorder (MDD) are two of the most common and severe mental disorders, the etiologies of which are not yet clearly elucidated. The ACSM1 gene has been identified as a susceptibility gene for SCZ in two previous genome-wide association studies (GWAS). ACSM1 catalyzes the activation of fatty acids and plays an important role in the metabolic system. Some evidence has suggested that ACSM1 contributes to a genetic risk for MDD. The present study aimed to evaluate the common genetic risk of the ACSM1 gene in these two disorders in the Han Chinese population. In total, 1235 patients with SCZ, 1045 patients with MDD and 1235 control subjects of Chinese origin were recruited. Six single nuclear polymorphisms (SNPs) in ACSM1 were genotyped to test their associations with SCZ and MDD. SNP rs163234 was found to be significantly associated with both SCZ (permutated Pallele=1.700×10(-3), OR=1.350 [95% CI=1.152-1.581]) and MDD (permutated Pallele=4.800×10(-3), OR=1.329 [95% CI=1.127-1.567]). SNP rs433598 showed a strong association with SCZ (permutated Pallele=4.300×10(-3), OR=1.303 [95% CI=1.117-1.520]). Haplotype analysis of the blocks containing the two positive markers also revealed a significant association. This is the first study to assess the possible association of the ACSM1 gene with a genetic susceptibility for MDD. Our data are the first to suggest a positive association of the ACSM1 gene with a genetic susceptibility for SCZ and MDD in the Han Chinese population.

Objective Synaptosomal-associated protein of 25 kDa (SNAP25) is a member of the soluble N-ethylmaleimide-sensitive factor attachment receptor (SNARE) protein complex, which plays essential roles in the modulation of different voltage-gated calcium channels and neurotransmitter release. Many previous studies have reported the SNAP25 gene to be significantly associated with attention-deficit/hyperactivity disorder (ADHD). Recently, shared genetic variants have been demonstrated in 5 major psychiatric disorders, including schizophrenia, major depressive disorder, bipolar disorder, autism spectrum disorders, and ADHD. However, no compelling, convincing evidence has suggested an association between SNAP25 and schizophrenia or major depressive disorder. Thus, we investigated the association between SNAP25 and both schizophrenia and major depressive disorder in the Han Chinese population. Method We performed a large-scale case-control study to test the association between SNAP25 and 2 major mental disorders, schizophrenia (DSM-IV criteria) and major depressive disorder (DSM-IV criteria), in the Han Chinese population. Seven single-nucleotide polymorphisms (SNPs) were genotyped in 1,330 schizophrenia patients, 1,045 major depressive disorder patients, and 1,520 healthy controls of Han Chinese origin. Results Two SNPs, rs3787283 and rs3746544, were found to be associated with both schizophrenia (rs3746544, adjusted P = .00257) and major depressive disorder (rs3746544, adjusted P = .0485; rs3787283, adjusted P = .00387) in this study. The AG haplotype consisting of rs3787283 and rs3746544 was also significantly associated with both schizophrenia and major depressive disorder (schizophrenia: adjusted P = .0126; major depressive disorder: adjusted P = .000580). Additionally, we carried out a meta-analysis of the current data and published association results and further confirmed the association between rs3746544 and schizophrenia (Pmeta = .002, ORmeta = 1.213 [95% CI, 1.077-1.367]). Conclusions Our results indicated that SNPs in SNAP25 represented a common risk factor of both schizophrenia and major depressive disorder in the Han Chinese population.

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.

As a major extracellular matrix component, ITIHs played an important role in inflammation and carcinogenesis. Several genome-wide association studies have reported that some positive signals which were derived from the tight linkage disequilibrium region on chromosome 3p21 were associated with both schizophrenia and bipolar disorders in the Caucasian population. To further investigate whether this genomic region is also a susceptibility locus of schizophrenia and major depressive disorder in the Han Chinese population, we conducted this study by recruiting 1235 schizophrenia patients, 1045 major depressive disorder patients and 1235 healthy control subjects in the Han Chinese samples for a case-control study. We genotyped seven SNPs within this region using TaqMan® technology. We found that rs2710322 was significantly associated with schizophrenia (adjusted P(allele) = 0.0018, adjusted P(genotype) = 0.006, OR [95% CI] = 1.278 [1.117-1.462]) while rs1042779 was weakly associated with schizophrenia (adjusted P(allele) = 0.048, OR [95% CI] = 1.164 [1.040-1.303]) and major depressive disorder (adjusted P(allele) = 0.042, OR [95% CI] = 1.178 [1.047-1.326]); it was also our finding that rs3821831 was positively associated with major depressive disorder (adjusted P(allele) = 0.003, adjusted P(genotype) = 0.006, OR [95% CI] = 1.426 [1.156-1.760]). Furthermore, no haplotype was found to be associated with schizophrenia and major depressive disorder. Via the association analysis which combines the schizophrenia and major depressive disorder cases, we also notice that rs1042779 and rs3821831 were significantly associated with combined cases (rs1042779: adjusted P(allele) = 0.012, adjusted P(genotype) = 0.018, OR [95% CI] = 1.171 [1.060-1.292]; rs3821831:adjusted P(genotype) = 0.012, OR [95% CI] = 1.193 [1.010-1.410]). Our results revealed that the shared genetic risk factors of both schizophrenia and major depressive disorder exist in ITIH family genes in the Han Chinese population.

BackgroundCommon psychiatric disorders are highly heritable, indicating that genetic factors play an important role in their aetiology. TheCACNA1Cgene, which codes for subunit alpha-1C of the Cav1.2 voltage-dependent L-type calcium channel, has been consistently found to be the shared risk gene for several kinds of mental disorder.AimsTo investigate whetherCACNA1Cis a susceptibility gene for schizophrenia and major depressive disorder in the Han Chinese population.MethodWe carried out a case–control study of 1235 patients with schizophrenia, 1045 with major depressive disorder and 1235 healthy controls. A tag single nucleotide polymorphism (SNP) rs1006737 along with another 10 tag SNPs in theCACNA1Cgene were genotyped in all samples.ResultsWe found that rs1006737 was associated with both schizophrenia (Pallele= 0.0014,Pgenotype= 0.006, odds ratio (OR) = 1.384, 95% CI 1.134–1.690) and major depressive disorder (Pallele= 0.0007,Pgenotype= 0.003, OR = 1.425, 95% CI 1.160–1.752).ConclusionsOur findings supportCACNA1Cbeing a risk gene for both schizophrenia and major depressive disorder in the Han Chinese population.

N-ethyl-N-nitrosourea (ENU) mutagenesis has led to the elucidation of several regulator genes for melanocyte and skin development. Here we characterized a mutant from ENU mutagenesis with similar phenotype as that of Splotch mutant, including exencephaly, spina bifida and abnormal limbs in homozygotes as well as white belly spotting and occasionally loop-tail in heterozygotes. This novel mutant was named as Sp(xG). Through genome-wide linkage analysis in backcross progenies with microsatellite markers, the Sp(xG) was confined to a region between D1MIT415 and D1MIT7 on chromosome 1, where notable Pax3 gene was located. Direct sequencing revealed that Sp(xG) carried a nucleotide A894G missense transition in exon 6 of Pax3 gene that resulted in Asn to Asp substitution at amino acid 269 within the highly-conserved homeodomain (HD) DNA recognition module, which was the first point mutation found in this domain in mice. This N269D mutation impaired the transactivation capacity of Pax3 protein, but exerted no effect on Pax3 protein translation. The characterization of the new mutation expanded our understanding the transactivation and DNA-binding structure of Pax3 protein.

Metabotropic glutamate receptor type 7 (GRM7) and type 8 (GRM8) are involved in the neurotransmission of glutamate which is supposed to play an important role in the development of schizophrenia (SCZ) and major depressive disorders (MDD). We designed this study to investigate whether common DNA variants or their genetic interactions within GRM7 and GMR8 genes were associated with these disorders in the Han Chinese population. Fourteen SNPs in GRM7 and GRM8 were selected within a sample set comprising 1235 SCZ patients, 1045 MDD patients and 1235 normal controls. Significant association in SCZ case-control subjects was observed for rs2229902 (permutated Pallele=0.0005, OR=1.492 [95% CI=1.231-1.807]) and rs9870680 (permutated Pallele=0.0023, OR=1.262 [95% CI=1.116-1.426]) in GRM7 and rs2237781 (permutated Pallele=0.0027, OR=1.346 [95% CI=1.149-1.575]) in GRM8. Association analysis for MDD case-control subjects revealed positive results in rs779706 (permutated Pallele=0.0099, OR=1.237 [95% CI=1.093-1.399]) of GRM7 and in rs1361995 (permutated Pallele=0.0017, OR=1.488 [95% CI=1.215-1.823]) of GRM8. Moreover, a three-locus model, constituted by polymorphisms in GRM7 and GRM8 significantly correlated with MDD in the gene-gene interaction analysis. Meta-analysis and haplotype analysis further confirmed our significant results. We demonstrated the genetic association of GRM7 and GRM8 with SCZ and MDD in the Han Chinese population. We also found susceptibility interactive effects of these two genes with both psychiatric disorders, which might provide new insights into the etiology of them.

Synaptosomal-associated protein of 25 kDa (SNAP25) is a member of the soluble N-ethylmaleimide-sensitive factor attachment receptor (SNARE) protein complex, which plays essential roles in the modulation of different voltage-gated calcium channels and neurotransmitter release. Many previous studies have reported the SNAP25 gene to be significantly associated with attention-deficit/hyperactivity disorder (ADHD). Recently, shared genetic variants have been demonstrated in 5 major psychiatric disorders, including schizophrenia, major depressive disorder, bipolar disorder, autism spectrum disorders, and ADHD. However, no compelling, convincing evidence has suggested an association between SNAP25 and schizophrenia or major depressive disorder. Thus, we investigated the association between SNAP25 and both schizophrenia and major depressive disorder in the Han Chinese population.We performed a large-scale case-control study to test the association between SNAP25 and 2 major mental disorders, schizophrenia (DSM-IV criteria) and major depressive disorder (DSM-IV criteria), in the Han Chinese population. Seven single-nucleotide polymorphisms (SNPs) were genotyped in 1,330 schizophrenia patients, 1,045 major depressive disorder patients, and 1,520 healthy controls of Han Chinese origin.Two SNPs, rs3787283 and rs3746544, were found to be associated with both schizophrenia (rs3746544, adjusted P = .00257) and major depressive disorder (rs3746544, adjusted P = .0485; rs3787283, adjusted P = .00387) in this study. The AG haplotype consisting of rs3787283 and rs3746544 was also significantly associated with both schizophrenia and major depressive disorder (schizophrenia: adjusted P = .0126; major depressive disorder: adjusted P = .000580). Additionally, we carried out a meta-analysis of the current data and published association results and further confirmed the association between rs3746544 and schizophrenia (Pmeta = .002, ORmeta = 1.213 [95% CI, 1.077-1.367]).Our results indicated that SNPs in SNAP25 represented a common risk factor of both schizophrenia and major depressive disorder in the Han Chinese population.

BackgroundPsychiatric disorders such as schizophrenia and major depressive disorder (MDD) are likely to be caused by multiple susceptibility genes, each with small effects in increasing the risk of illness. Identifying DNA variants associated with schizophrenia and MDD is a crucial step in understanding the pathophysiology of these disorders.AimsTo investigate whether theSP4gene plays a significant role in schizophrenia or MDD in the Han Chinese population.MethodWe focused on nine single nucleotide polymorphisms (SNPs) harbouring theSP4gene and carried out case–control studies in 1235 patients with schizophrenia, 1045 patients with MDD and 1235 healthy controls recruited from the Han Chinese population.ResultsWe found that rs40245 was significantly associated with schizophrenia in both allele and genotype distributions (Pallele= 0.0005,Pallele= 0.004 after Bonferroni correction;Pgenotype= 0.0023,Pgenotype= 0.0184 after Bonferroni correction). The rs6461563 SNP was significantly associated with schizophrenia in the allele distributions (Pallele= 0.0033,Pallele= 0.0264 after Bonferroni correction).ConclusionsOur results suggest that common risk factors in theSP4gene are associated with schizophrenia, although not with MDD, in the Han Chinese population.

Cadherin-7 (CDH7) gene encodes a calcium dependent cell-cell adhesion glycoprotein. Gene loci of cadherins family have been supposed to be involved in the pathogenesis of psychiatric disorders. Recent genome-wide association study also demonstrated that CDH7 was significant associated with bipolar disorder. Due to the fact that the same genetic risk factor can be shared by different kinds of psychiatric disorders, we examined whether CDH7 is also associated with major depressive disorder (MDD) in this study, with a large Han Chinese sample set. We carried out a 2-stage case-control study to examine the association between CDH7 and MDD in the Han Chinese population. Ten tag SNPs were genotyped using Taqman technology in 1,045 MDD patients and 1,520 healthy controls. Single-nucleotide polymorphisms with significance were additionally genotyped in another independent sample set with 576 MDD cases and 576 healthy controls. Among ten genotyped SNPs, rs1444067 and rs12605720 was found to be significantly associated with MDD (rs1444067: P(allele) = 0.00571, OR 0.830, 95 % CI 0.728-0.947; rs12605720: P(allele) = 0.00321, OR 1.245, 95 % CI 1.076-1.441). We successfully replicated these two SNPs association with independent sample sets (rs1444067: P(allele) = 0.00518; rs12605720: P(allele) = 0.0227). Finally we have combined these results by a meta-analysis (rs1444067: P(allele) = 0.000174, OR 0.817; rs12605720: P(allele) = 0.000199, OR 1.255). Our results support CDH7 to be a risk factor of MDD in the Han Chinese population. However, further studies with more markers and independent samples were suggested to validate our findings.

Background Refractive errors and high myopia are the most common ocular disorders, and both of them are leading causes of blindness in the world. Recently, genetic association studies in European and Japanese population identified that common genetic variations located in 15q14 and 15q25 were associated with high myopia. To validate whether the same variations conferred risk to high myopia in the Han Chinese population, we genotyped 1,461 individuals (940 controls and 521 cases samples) recruited of Han Chinese origin. Result We found rs8027411 in 15q25 (P = 0.012 after correction, OR = 0.78) was significantly associated with high myopia but rs634990 in 15q14 (P = 0.54 after correction), OR = 0.88) was not. Conclusions Our findings supported that 15q25 is a susceptibility locus for high myopia, and gene RASGRF1 was possible to play a role in the pathology of high myopia.