The Contribution of Mosaic Chromosomal Alterations to Schizophrenia.

BACKGROUND: Mosaic chromosomal alterations (mCAs) are implicated in neuropsychiatric disorders, yet the contribution to schizophrenia (SCZ) risk for somatic copy number variations (sCNVs) emerging in early developmental stages is not fully established. METHODS: We analyzed blood-derived genotype arrays from 9,715 SCZ patients and 28,822 controls of Chinese descent using a computational tool (MoChA) based on long-range chromosomal information to detect mCAs. We focused on probable early developmental sCNVs through stringent filtering. We assessed the sCNVs' burden across varying cell fraction (CF) cutoffs, as well as the frequency with which genes were involved in sCNVs. We integrated this data with the Psychiatric Genomics Consortium (PGC) dataset, which comprises 12,834 SCZ cases and 11,648 controls of European descent, and complemented it with genotyping data from postmortem brain tissue of 936 subjects (449 cases and 487 controls). RESULTS: Patients with SCZ had a significantly higher somatic losses detection rate than control subjects (1.00% vs 0.52%; odds ratio (OR) = 1.91; 95% CI, 1.47-2.49; two-sided Fisher's exact test, p=1.49×10-6). Further analysis indicated that the ORs escalated proportionately (from 1.91 to 2.78) with the increment in CF cutoffs. Recurrent sCNVs associated with SCZ (OR>8; Fisher's exact test, p<0.05) were identified, including notable regions at 10q21.1 (ZWINT), 3q26.1 (SLITRK3), 1q31.1 (BRINP3) and 12q21.31-21.32 (MGAT4C and NTS) in the Chinese cohort, some regions validated with PGC data. Cross-tissue validation pinpointed somatic losses at loci like 1p35.3-35.2 and 19p13.3-13.2. CONCLUSIONS: The study highlights mCAs' significant impact on SCZ, suggesting their pivotal role in the disorder's genetic etiology.

Genetic analysis of common variants in the ZNF804A gene with schizophrenia and major depressive disorder.

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.

Genome-wide association analysis identifies 30 new susceptibility loci for schizophrenia.

We conducted a genome-wide association study (GWAS) with replication in 36,180 Chinese individuals and performed further transancestry meta-analyses with data from the Psychiatry Genomics Consortium (PGC2). Approximately 95% of the genome-wide significant (GWS) index alleles (or their proxies) from the PGC2 study were overrepresented in Chinese schizophrenia cases, including ∼50% that achieved nominal significance and ∼75% that continued to be GWS in the transancestry analysis. The Chinese-only analysis identified seven GWS loci; three of these also were GWS in the transancestry analyses, which identified 109 GWS loci, thus yielding a total of 113 GWS loci (30 novel) in at least one of these analyses. We observed improvements in the fine-mapping resolution at many susceptibility loci. Our results provide several lines of evidence supporting candidate genes at many loci and highlight some pathways for further research. Together, our findings provide novel insight into the genetic architecture and biological etiology of schizophrenia.

The YWHAE gene confers risk to major depressive disorder in the male group of Chinese Han population.

Schizophrenia and major depressive disorder are two major psychiatric illnesses that may share specific genetic risk factors to a certain extent. Increasing evidence suggests that the two disorders might be more closely related than previously considered. To investigate whether YWHAE gene plays a significant role in major depressive disorder in Han Chinese population, we recruited 1135 unrelated major depressive disorder patients (485 males, 650 females) and 989 unrelated controls (296 males, 693 females) of Chinese Han origin. Eleven common SNPs were genotyped using TaqMan® technology. In male-group, the allele and genotype frequencies of rs34041110 differed significantly between patients and control (Pallele=0.036486, OR[95%CI]: 1.249442(1.013988-1.539571); Pgenotype=0.045301). Also in this group, allele and genotype frequencies of rs1532976 differed significantly (Pallele=0.013242, OR[95%CI]: 1.302007(1.056501-1.604563); genotype: P=0.039152). Haplotype-analyses showed that, in male-group, positive association with major depressive disorder was found for the A-A-C-G haplotype of rs3752826-rs2131431-rs1873827-rs12452627 (χ2=20.397, P=6.38E-06, OR[95%CI]: 7.442 [2.691-20.583]), its C-A-C-G haplotype (χ2=19.122, P=1.24E-05, OR and 95%CI: 0.402 [0.264-0.612]), its C-C-T-G haplotype (χ2=9.766, P=0.001785, OR[95%CI]: 5.654 [1.664-19.211]). In female-group, positive association was found for the A-A-C-G haplotype of rs3752826-rs2131431-rs1873827-rs12452627 (χ2=78.628, P=7.94E-19, OR[95%CI]: 50.043 [11.087-225.876]), its A-C-T-G haplotype (χ2=38.806, P=4.83E-10, OR[95%CI]: 0.053 [0.015-0.192]), the C-A-C-G haplotype (χ2=18.930, P=1.37E-05, OR[95%CI]: 0.526 [0.392-0.705]), and the C-C-T-G haplotype (χ2=38.668, P=5.18E-10, OR[95%CI]: 6.130 [3.207-11.716]). Our findings support YWHAE being a risk gene for Major Depressive Disorder in the Han Chinese population.

An Engineered Rare Codon Device for Optimization of Metabolic Pathways.

Rare codons generally arrest translation due to rarity of their cognate tRNAs. This property of rare codons can be utilized to regulate protein expression. In this study, a linear relationship was found between expression levels of genes and copy numbers of rare codons inserted within them. Based on this discovery, we constructed a molecular device in Escherichia coli using the rare codon AGG, its cognate tRNA (tRNA(Arg) (CCU)), modified tRNA(Asp) (GUC → CCU), and truncated aspartyl-tRNA synthetase (TDRS) to switch the expression of reporter genes on or off as well as to precisely regulate their expression to various intermediate levels. To underscore the applicability of our work, we used the rare codon device to alter the expression levels of four genes of the fatty acid synthesis II (FASII) pathway (i.e. fabZ, fabG, fabI, and tesA') in E. coli to optimize steady-state kinetics, which produced nearly two-fold increase in fatty acid yield. Thus, the proposed method has potential applications in regulating target protein expression at desired levels and optimizing metabolic pathways by precisely tuning in vivo molar ratio of relevant enzymes.

Genome-wide Analysis of the Role of Copy Number Variation in Schizophrenia Risk in Chinese.

BACKGROUND: Compelling evidence suggested the role of copy number variations (CNVs) in schizophrenia susceptibility. Most of the evidence was from studies in populations with European ancestry. We tried to validate the associated CNV loci in a Han Chinese population and identify novel loci conferring risk of schizophrenia. METHODS: We performed a genome-wide CNV analysis on 6588 patients with schizophrenia and 11,904 control subjects of Han Chinese ancestry. RESULTS: Our data confirmed increased genome-wide CNV (>500 kb and <1%) burden in schizophrenia, and the increasing trend was more significant when only >1 Mb CNVs were considered. We also replicated several associated loci that were previously identified in European populations, including duplications at 16p11.2, 15q11.2-13.1, 7q11.23, and VIPR2 and deletions at 22q11.2, 1q21.1-q21.2, and NRXN1. In addition, we discovered three additional new potential loci (odds ratio >6, p < .05): duplications at 1p36.32, 10p12.1, and 13q13.3, involving many neurodevelopmental and synaptic related genes. CONCLUSIONS: Our findings provide further support for the role of CNVs in the etiology of schizophrenia.

Role played by the SP4 gene in schizophrenia and major depressive disorder in the Han Chinese population.

BACKGROUND: Psychiatric 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. AIMS: To investigate whether the SP4 gene plays a significant role in schizophrenia or MDD in the Han Chinese population. METHOD: We focused on nine single nucleotide polymorphisms (SNPs) harbouring the SP4 gene 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. RESULTS: We 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). CONCLUSIONS: Our results suggest that common risk factors in the SP4 gene are associated with schizophrenia, although not with MDD, in the Han Chinese population.

Significant association of GRM7 and GRM8 genes with schizophrenia and major depressive disorder in the Han Chinese population.

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.

Loci with genome-wide associations with schizophrenia in the Han Chinese population.

BACKGROUND: A large schizophrenia genome-wide association study (GWAS) and a subsequent extensive replication study of individuals of European ancestry identified eight new loci with genome-wide significance and suggested that the MIR137-mediated pathway plays a role in the predisposition for schizophrenia. AIMS: To validate the above findings in a Han Chinese population. METHOD: We analysed the single nucleotide polymorphisms (SNPs) in the newly identified schizophrenia candidate loci and predicted MIR137 target genes based on our published Han Chinese populations (BIOX) GWAS data. We then analysed 18 SNPs from the candidate regions in an independent cohort that consisted of 3585 patients with schizophrenia and 5496 controls of Han Chinese ancestry. RESULTS: We replicated the associations of five markers (P<0.05), including three that were located in the predicted MIR137 target genes. Two loci (ITIH3/4: rs2239547, P = 1.17 × 10(-10) and CALN1: rs2944829, P = 9.97 × 10(-9)) exhibited genome-wide significance in the Han Chinese population. CONCLUSIONS: The ITIH3/4 locus has been reported to be of genome-wide significance in the European population. The successful replication of this finding in a different ethnic group provides stronger evidence for the association between schizophrenia and ITIH3/4. We detected the first genome-wide significant association of schizophrenia with CALN1, which is a predicted target of MIR137, and thus provide new evidence for the associations between MIR137 targets and schizophrenia.

Genetic association of ACSM1 variation with schizophrenia and major depressive disorder in the Han Chinese population.

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.

SLC17A7 gene may be the indicator of selective serotonin reuptake inhibitor treatment response in the Chinese Han population.

Selective serotonin reuptake inhibitors (SSRIs) are widely used drugs for major depressive disorder (MDD), although the treatment outcomes vary in different people. The vesicular glutamate transporter 1 coded by SLC17A7 gene has been reported associated with MDD. According to its role in glutamate transmission, it is reasonable to consider it as a potential pharmacogenetic candidate in SSRI treatment. A total of 290 MDD patients who had been taking SSRIs for 6 weeks were recruited. Their genotypes were assessed for the presence of 4 single-nucleotide polymorphisms, which were selected from either the HapMap Chinese ethnic group or the literature report. Treatment effects were evaluated by the change rate of Hamilton Rating Scale for Depression. After the adjustment for the false discovery rate, 1 single-nucleotide polymorphism (rs74174284, false discovery rate; P = 0.032) demonstrated significant association with SSRI treatment response at week 6. Our results suggest that genetic variants in the SLC17A7 gene may be indicators of treatment response in MDD patients treated by SSRIs.

Common variants in the CDH7 gene are associated with major depressive disorder 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.

A pharmacogenetic study of risperidone on chemokine (C-C motif) ligand 2 (CCL2) in Chinese Han schizophrenia patients.

Previous observations of the pathophysiological distribution and pharmacological profile of the chemokine (C-C motif) ligand 2 (CCL2) have indicated its potential role in antipsychotic drug actions. More information on the pharmacogenetics of CCL2 may therefore be useful in developing individualized therapy. However, to our knowledge, rare studies have been reported in this area. This investigation was attempted to clarify whether CCL2 polymorphism could affect risperidone efficacy. We genotyped four SNPs (rs4795893, rs1024611, rs4586 and rs2857657) distributed throughout the CCL2 gene and examined them for association using the Positive and Negative Syndrome Scale (PANSS) score in two independent cohorts of Chinese schizophrenic patients (n = 208) from two different geographic areas, following an 8-week period of risperidone monotherapy. We found that all genotyped SNPs were significantly associated with risperidone treatment (rs4795893: p = 1.66E-04, rs4586: p = 0.001, rs2857657: p = 0.004, at week 4, in ANOVA). Our results indicate that there may be some effect of variations in the CCL2 gene on therapeutic efficacy of risperidone, and the associated polymorphisms may be a potential genetic marker for predicting the therapeutic effect of risperidone.

DNA methylation profiling in the thalamus and hippocampus of postnatal malnourished mice, including effects related to long-term potentiation.

BACKGROUND: DNA methylation has been viewed as the most highly characterized epigenetic mark for genome regulation and development. Postnatal brains appear to exhibit stimulus-induced methylation changes because of factors such as environment, lifestyle, and diet (nutrition). The purpose of this study was to examine how extensively the brain DNA methylome is regulated by nutrition in early life. RESULTS: By quantifying the total amount of 5-methylcytosine (5mC) in the thalamus and the hippocampus of postnatal malnourished mice and normal mice, we found the two regions showed differences in global DNA methylation status. The methylation level in the thalamus was much higher than that in the hippocampus. Then, we used a next-generation sequencing (NGS)-based method (MSCC) to detect the whole genome methylation of the two regions in malnourished mice and normal mice. Notably, we found that in the thalamus, 500 discriminable variations existed and that approximately 60% were related to neuronal development or psychiatric diseases. Pathway analyses of the corresponding genes highlighted changes for 9 genes related to long-term potentiation (5.3-fold enrichment, P = 0.033). CONCLUSIONS: Our findings may help to indicate the genome-wide DNA methylation status of different brain regions and the effects of malnutrition on brain DNA methylation. The results also indicate that postnatal malnutrition may increase the risk of psychiatric disorders.

ITIH family genes confer risk to 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.

CACNA1C, schizophrenia and major depressive disorder in the Han Chinese population.

BACKGROUND: Common psychiatric disorders are highly heritable, indicating that genetic factors play an important role in their aetiology. The CACNA1C gene, 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. AIMS: To investigate whether CACNA1C is a susceptibility gene for schizophrenia and major depressive disorder in the Han Chinese population. METHOD: We 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 the CACNA1C gene were genotyped in all samples. RESULTS: We found that rs1006737 was associated with both schizophrenia (P(allele) = 0.0014, P(genotype) = 0.006, odds ratio (OR) = 1.384, 95% CI 1.134-1.690) and major depressive disorder (P(allele) = 0.0007, P(genotype) = 0.003, OR = 1.425, 95% CI 1.160-1.752). CONCLUSIONS: Our findings support CACNA1C being a risk gene for both schizophrenia and major depressive disorder in the Han Chinese population.

ABCB6, ABCB1 and ABCG1 genetic polymorphisms and antidepressant response of SSRIs in Chinese depressive patients.

AIM: Major depressive disorder is a common psychiatric disorder with worldwide prevalence. The most widely prescribed antidepressants are selective serotonin reuptake inhibitors (SSRIs). ATP-binding cassette proteins are responsible for the membrane transport of various molecules including antidepressive drugs. We investigated whether SNPs in ABCB6, ABCB1 and ABCG1 were associated with the treatment response of SSRIs. MATERIALS & METHODS: A pharmacogenetic study genotyping nine SNPs was conducted in 290 major depressive disorder patients in the Chinese Han population. Allele and genotype frequencies were compared between responders and nonresponders. RESULTS: The allele frequencies of rs28401781 and rs4148739 in ABCB1 showed significant difference between responders and nonresponders before correction (p = 0.0297 and p = 0.0359, respectively). No significant associations were detected for the ABCB6 or ABCG1 gene. CONCLUSION: Our results suggest that ABCB1 polymorphisms might be associated with SSRIs treatment response in the Chinese Han population.

Identification of aberrant microRNA expression pattern in pediatric gliomas by microarray.

BACKGROUND: Brain tumor remains the leading cause of disease-related death in children. Many studies have focused on the complex biological process involved in pediatric brain tumors but little is know about the possible role of microRNAs in the genesis of these tumors. METHODS: In this study, we used a microRNA microarray assay to study the expression pattern of microRNAs in pediatric gliomas and matched normal tissues. RESULTS: We found 40 differentially expressed microRNAs, among which miR-1321, miR-513b, miR-769-3p were found be related to cancer genesis for the first time. The expression of selected microRNAs were then confirmed by qRT-PCR. Furthermore, GO and pathway analysis showed that the target genes of the 40 differentially expressed microRNAs were significantly enriched in nervous system-related and tumor-related biological processes and signaling pathways. Additionally, an apoptosis-related network of microRNA-mRNA interaction, representing the critical microRNAs and their targets, was constructed based on microRNA status. CONCLUSIONS: In the present study we identified the changed expression pattern of microRNAs in pediatric gliamas. Our study also provides a better understanding of pediatric brain tumor biology and may assist in the development of less toxic therapies and in the search for better markers for disease stratification. VIRTUAL SLIDES: The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/1323049861105720.

Association study on the DLG4 gene and schizophrenia in the Chinese Han population.

BACKGROUND: Abnormal expressions of the N-methyl-D-aspartate receptor and its interacting postsynaptic density (PSD) molecules have been hypothesized to be involved in the pathophysiology of schizophrenia. Few studies have carried out association studies with DLG4 gene (coding PSD-95 protein) and sought to validate the results with Asian schizophrenia patients. PATIENTS AND METHODS: To further investigate the significance of DLG4 in Asian schizophrenic patients, we examined seven single-nucleotide polymorphisms (SNPs) within this gene in 1504 unrelated Chinese mainland individuals (893 patients and 611 controls). RESULTS: No association was found between these seven SNPs and schizophrenia within our sample. No significant differences in allele or genotype frequencies between schizophrenic paranoid patients and controls were found. CONCLUSION: Although no allelic or genotypic variances of this gene were observed, the possibility that SNPs within DLG4 represent a positive schizophrenia risk gene cannot be excluded. Our research provided a reference for further research into this gene in other populations.

Histamine H4 receptor polymorphism: a potential predictor of risperidone efficacy.

Histamine interacts with histamine H4 receptor (HRH4) to impact antipsychotic response. Pharmacogenetic information about this receptor could therefore be useful in developing individualized therapy. The aim of this investigation was to clarify whether polymorphisms at human HRH4 gene alter risperidone efficacy. We genotyped 5 tag-single nucleotide polymorphisms of the HRH4 gene and analyzed their association with the reduction in Positive and Negative Syndrome Scale (PANSS) scores in a group of 113 Chinese Han patients with schizophrenia who were following an 8-week period of risperidone monotherapy. Using χ(2), analysis of variance, haplotype, and receiver operating characteristics analysis, we found that HRH4 common variant rs4483927 is significantly associated with risperidone efficacy and that its TT genotype predicts poor therapeutic response both on the positive, negative, and general subscales and on the total scale of PANSS scores (P = 0.017, 0.019, 0.021, and 0.002, respectively, in analysis of variance). Our results provide the first evidence that an HRH4 polymorphism may be a molecular marker for the prediction of risperidone efficacy and suggest novel pharmacologic links between HRH4 gene and treatment of schizophrenia.