Dai Zhang

Publications (65)241.29 Total impact

• Article: Myosin Vb gene is associated with schizophrenia in Chinese Han population.

  Yaguang Chen, Lin Tian, Fuquan Zhang, Chenxing Liu, Tianlan Lu, Yanyan Ruan, Lifang Wang, Hao Yan, Jun Yan, Qi Liu, Hongyan Zhang, Wenbin Ma, Jianli Yang, Keqing Li, Luxian Lv, Dai Zhang, Weihua Yue
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  ABSTRACT: Myosin Vb (MYO5B) has recently been implicated in the etiology of bipolar disorder in a genome-wide association study (GWAS). This gene is involved in amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA) receptor subunit glutamate receptor 1 (GluR1) recycling and plays an important role in the primary excitatory neurotransmission. Dysfunction of the brain glutamate system has been postulated to be involved in the pathophysiology in schizophrenia. To further investigate the association between MYO5B polymorphisms and schizophrenia, we genotyped nine single nucleotide polymorphisms (SNPs) in an independent sample of 1463 individuals with schizophrenia and 1563 healthy control subjects, and detected three SNPs and two haplotype blocks which displayed significant association with schizophrenia. This association was further strengthened by the results of meta-analysis. Our data strongly supported that the MYO5B gene might be associated with schizophrenia in the Chinese Han population and they have implications for understanding the glutamate hypothesis of schizophrenia.
  Psychiatry research. 04/2013;
• Article: Association study between genes in Reelin signaling pathway and autism identifies DAB1 as a susceptibility gene in a Chinese Han population.

  Jun Li, Jing Liu, Linnan Zhao, Yuanlin Ma, Meixiang Jia, Tianlan Lu, Yanyan Ruan, Qizhai Li, Weihua Yue, Dai Zhang, Lifang Wang
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  ABSTRACT: Autism is a pervasive neurodevelopmental disorder diagnosed in early childhood. The genetic factors might play an important role in its pathogenesis. Previous studies revealed that Reelin (RELN) polymorphisms were associated with autism. However, the roles of genes in Reelin signaling pathway for autism are largely unknown. As several knockout mice models in which the Reelin pathway genes (i.e. DAB1, VLDLR/APOER2, FYN/SRC and CRK/CRKL) are deficient have the similar phenotype as the reeler mice (Reelin(-/-)), we hypothesized that the Reelin signaling pathway genes might play roles in the etiology of autism. Therefore, we conducted a family-based association study. Sixty-two tagged single nucleotide polymorphisms (SNPs) covering 15 genes in Reelin pathway were genotyped in 239 trios, and 14 significant SNPs were further investigated in the additional 188 trios. In total 427 trios, we found significant genetic association between autism and four SNPs in DAB1 (rs12035887 G: p=0.0006; rs3738556 G: p=0.0044; rs1202773 A: p=0.0048; rs12740765 T: p=0.0196). After the Bonferroni correction, SNP rs12035887 remained significant. Furthermore, the haplotype constructed with rs1202773 and rs12023109 in DAB1 showed significant excess transmission in both individual and global haplotype analyses (p=0.0052 and 0.0279, respectively). Our findings suggested that variations in DAB1 involved in the Reelin signaling pathway might contribute to genetic susceptibility to autism with Chinese Han decent, supporting the defect in the Reelin signaling pathway as a predisposition factor for autism.
  Progress in Neuro-Psychopharmacology and Biological Psychiatry 01/2013; · 3.25 Impact Factor
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  Available from: Hao Yan

  Article: Association of MTHFR C677T polymorphism with schizophrenia and its effect on episodic memory and gray matter density in patients.

  Yanling Zhang, Hao Yan, Lin Tian, Fang Wang, Tianlan Lu, Lifang Wang, Jun Yan, Qi Liu, Lan Kang, Yanyan Ruan, Dai Zhang, Weihua Yue
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  ABSTRACT: Growing evidence suggests that the methylenetetrahydrofolate reductase (MTHFR) may play a role in the pathogenesis of schizophrenia. Recent studies suggested that the MTHFR 677T, as a risk allele, has an impact on brain activation and memory function in schizophrenia patients. To confirm further the association between this functional polymorphism and schizophrenia, we detected genotypes of MTHFR C677T polymorphism in 1,002 schizophrenic patients and 1,036 controls of Chinese Han population, by using direct DNA sequencing method. To explore further effects of MTHFR C677T polymorphism on memory and brain function in schizophrenia, 33 schizophrenia patients and 29 healthy participants were selected from above samples to be assessed with MRI scanning and episodic memory (EM) examination. The case - control association study results showed that the MTHFR C677T was associated with schizophrenia (χ(2)=14.11, P=1.74×10(-4), OR=0.79; 95% CI=0.70 - 0.89). We also found that the MTHFR 677T allele had a load-dependent effect on EM in schizophrenic patients, but not in healthy control participants. Further analysis on gray matter density (GMD) revealed significant diagnostic effects in bilateral frontal cortices, bilateral insula, left medial temporal cortex and bilateral occipital cortices, effects of MTHFR genotype in the right insula, right inferior frontal gyrus, right rolandic opercula, right parahippocampal gyrus and right medial temporal pole, and effects of genotype-diagnosis interaction in the right temporal gyrus. Our findings suggested that the MTHFR 677T allele might have effect on risk of schizophrenia, memory impairment and GMD changes in patients.
  Behavioural brain research 01/2013; · 3.22 Impact Factor
• Article: Association study of NRXN3 polymorphisms with schizophrenia and risperidone-induced bodyweight gain in Chinese Han population.

  Xiaofeng Hu, Jishui Zhang, Chao Jin, Weifeng Mi, Fang Wang, Wenbin Ma, Cuicui Ma, Yongfeng Yang, Wenqiang Li, Hongxing Zhang, Bo Du, Keqing Li, Chenxing Liu, Lifang Wang, Tianlan Lu, Hongyan Zhang, Luxian Lv, Dai Zhang, Weihua Yue
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  ABSTRACT: Recent researches have implicated that mutations in the neurexin-3 (NRXN3) gene on chromosome 14q24.3-q31.1 might play a role in addiction, autism, and obesity. In order to explore the association of NRXN3 polymorphisms with schizophrenia, we examined seven single nucleotide polymorphisms (SNPs) in NRXN3 spanning 1.33Mb of this gene, in a Chinese Han sample of 1,214 schizophrenic patients and 1,517 healthy control subjects. Our results showed that three SNPs were associated with schizophrenia (rs7157669: A>C, p=0.006; rs724373: C>T, p=0.014; rs7154021: C>T, p=0.018). After corrected for multiple tests, the association of rs7157669 remained significant but those for two others were modest. According to the linkage disequilibrium pattern, the 7 SNPs may construct 3 haplotype blocks. Several haplotypes were significantly associated with schizophrenia, constructed by rs11624704-rs7157669- rs724373 (AAC, p=0.003; ACT, p=0.007, both remained significant after permutation tests), rs7154021-rs7142344 (TT, p=0.024; CT, p=0.012), respectively. Among the patients, 326 ones at first onset have received 6-week monotherapy of risperidone. Further analyses showed that two SNPs were associated with percentage of bodyweight gain following a 6-week therapy of risperidone (rs11624704: p=0.03; rs7154021: p=0.008) and rs7154021 remained significant after permutation test. Our findings suggested that NRXN3 might represent a major susceptibility gene for schizophrenia and have a role in bodyweight gain related to therapy of risperidone in Chinese Han population.
  Progress in Neuro-Psychopharmacology and Biological Psychiatry 01/2013; · 3.25 Impact Factor
• Article: Sequencing ASMT Identifies Rare Mutations in Chinese Han Patients with Autism.

  Lifang Wang, Jun Li, Yanyan Ruan, Tianlan Lu, Chenxing Liu, Meixiang Jia, Weihua Yue, Jing Liu, Thomas Bourgeron, Dai Zhang
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  ABSTRACT: Melatonin is involved in the regulation of circadian and seasonal rhythms and immune function. Prior research reported low melatonin levels in autism spectrum disorders (ASD). ASMT located in pseudo-autosomal region 1 encodes the last enzyme of the melatonin biosynthesis pathway. A previous study reported an association between ASD and single nucleotide polymorphisms (SNPs) rs4446909 and rs5989681 located in the promoter of ASMT. Furthermore, rare deleterious mutations were identified in a subset of patients. To investigate the association between ASMT and autism, we sequenced all ASMT exons and its neighboring region in 398 Chinese Han individuals with autism and 437 healthy controls. Although our study did not detect significant differences of genotypic distribution and allele frequencies of the common SNPs in ASMT between patients with autism and healthy controls, we identified new rare coding mutations of ASMT. Among these rare variants, 4 were exclusively detected in patients with autism including a stop mutation (p.R115W, p.V166I, p.V179G, and p.W257X). These four coding variants were observed in 6 of 398 (1.51%) patients with autism and none in 437 controls (Chi-Square test, Continuity Correction p = 0.032, two-sided). Functional prediction of impact of amino acid showed that p.R115W might affect protein function. These results indicate that ASMT might be a susceptibility gene for autism. Further studies in larger samples are needed to better understand the degree of variation in this gene as well as to understand the biochemical and clinical impacts of ASMT/melatonin deficiency.
  PLoS ONE 01/2013; 8(1):e53727. · 4.09 Impact Factor
• Article: Replication of Association between Schizophrenia and Chromosome 6p21-6p22.1 Polymorphisms in Chinese Han Population.

  Yang Zhang, Tianlan Lu, Hao Yan, Yanyan Ruan, Lifang Wang, Dai Zhang, Weihua Yue, Lin Lu
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  ABSTRACT: Chromosome 6p21-p22.1, spanning the extended major histocompatibility complex (MHC) region, is a highly polymorphic, gene-dense region. It has been identified as a susceptibility locus of schizophrenia in Europeans, Japanese, and Chinese. In our previous two-stage genome-wide association study (GWAS), polymorphisms of zinc finger with KRAB and SCAN domains 4 (ZKSCAN4), nuclear factor-κB-activating protein-like (NKAPL), and piggyBac transposable element derived 1 (PGBD1), localized to chromosome 6p21-p22.1, were strongly associated with schizophrenia. To further investigate the association between polymorphisms at this locus and schizophrenia in the Chinese Han population, we selected eight other single-nucleotide polymorphisms (SNPs) distributed in or near these genes for a case-control association study in an independent sample of 902 cases and 1,091 healthy controls in an attempt to replicate the GWAS results. Four of these eight SNPs (rs12214383, rs1150724, rs3800324, and rs1997660) displayed a nominal difference in allele frequencies between the case and control groups. The association between two of these SNPs and schizophrenia were significant even after Bonferroni correction (rs12000: allele A>G, P = 2.50E-04, odds ratio [OR] = 1.27, 95% confidence interval [CI] = 1.12-1.45; rs1150722: allele C>T, P = 4.28E-05, OR = 0.55, 95% CI = 0.41-0.73). Haplotype ATTGACGC, comprising these eight SNPs (rs2235359, rs2185955, rs12214383, rs12000, rs1150724, rs1150722, rs3800324, and rs1997660), was significantly associated with schizophrenia (P = 6.60E-05). We also performed a combined study of this replication sample and the first-stage GWAS sample. The combined study revealed that rs12000 and rs1150722 were still strongly associated with schizophrenia (rs12000: allele G>A, P(combined) = 0.0019, OR = 0.81; rs1150722: allele G>A, P(combined) = 3.00E-04, OR = 0.61). These results support our findings that locus 6p21-p22.1 is significantly associated with schizophrenia in the Chinese Han population and encourage further studies of the functions of these genetic factors.
  PLoS ONE 01/2013; 8(2):e56732. · 4.09 Impact Factor
• Article: The Evidence for Association of ATP2B2 Polymorphisms with Autism in Chinese Han Population.

  Wen Yang, Jing Liu, Fanfan Zheng, Meixiang Jia, Linnan Zhao, Tianlan Lu, Yanyan Ruan, Jishui Zhang, Weihua Yue, Dai Zhang, Lifang Wang
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  ABSTRACT: Autism is a neurodevelopmental disorder with a high estimated heritability. ATP2B2, located on human chromosome 3p25.3, encodes the plasma membrane calcium-transporting ATPase 2 which extrudes Ca(2+) from cytosol into extracellular space. Recent studies reported association between ATP2B2 and autism in samples from Autism Genetic Resource Exchange (AGRE) and Italy. In this study, we investigated whether ATP2B2 polymorphisms were associated with autism in Chinese Han population. We performed a family based association study between five SNPs (rs35678 in exon, rs241509, rs3774180, rs3774179, and rs2278556 in introns) in ATP2B2 and autism in 427 autism trios of Han Chinese descent. All SNPs were genotyped using the Sequenom genotyping platform. The family-based association test (FBAT) program was used to perform association test for SNPs and haplotype analyses. This study demonstrated a preferential transmission of T allele of rs3774179 to affected offsprings under an additive model (T>C, Z = 2.482, p = 0.013). While C allele of rs3774179 showed an undertransmission from parents to affected children under an additive and a dominant model, respectively (Z = -2.482, p = 0.013; Z = -2.591, p = 0.0096). Haplotype analyses revealed that three haplotypes were significantly associated with autism. The haplotype C-C (rs3774180-rs3774179) showed a significant undertransmission from parents to affected offsprings both in specific and global haplotype FBAT (Z = -2.037, p = 0.042; Global p = 0.03). As for the haplotype constructed by rs3774179 and rs2278556, C-A might be a protective haplotype (Z = -2.206, p = 0.027; Global p = 0.04), while T-A demonstrated an excess transmission from parents to affected offsprings (Z = 2.143, p = 0.032). These results were still significant after using the permutation method to obtain empirical p values. Our research suggested that ATP2B2 might play a role in the etiology of autism in Chinese Han population.
  PLoS ONE 01/2013; 8(4):e61021. · 4.09 Impact Factor
• Article: MirSNP, a database of polymorphisms altering miRNA target sites, identifies miRNA-related SNPs in GWAS SNPs and eQTLs.

  Chenxing Liu, Fuquan Zhang, Tingting Li, Ming Lu, Lifang Wang, Weihua Yue, Dai Zhang
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  ABSTRACT: BACKGROUND: Numerous single nucleotide polymorphisms (SNPs) associated with complex diseases have been identified by genome-wide association studies (GWAS) and expression quantitative trait loci (eQTLs) studies. However, few of these SNPs have explicit biological functions. Recent studies indicated that the SNPs within the 3'UTR regions of susceptibility genes could affect complex traits/diseases by affecting the function of miRNAs. These 3'UTR SNPs are functional candidates and therefore of interest to GWAS and eQTL researchers.DescriptionWe developed a publicly available online database, MirSNP (http://cmbi.bjmu.edu.cn/mirsnp), which is a collection of human SNPs in predicted miRNA-mRNA binding sites. We identified 414,510 SNPs that might affect miRNA-mRNA binding. Annotations were added to these SNPs to predict whether a SNP within the target site would decrease/break or enhance/create an miRNA-mRNA binding site. By applying MirSNP database to three brain eQTL data sets, we identified four unreported SNPs (rs3087822, rs13042, rs1058381, and rs1058398), which might affect miRNA binding and thus affect the expression of their host genes in the brain. We also applied the MirSNP database to our GWAS for schizophrenia: seven predicted miRNA-related SNPs (p < 0.0001) were found in the schizophrenia GWAS. Our findings identified the possible functions of these SNP loci, and provide the basis for subsequent functional research. CONCLUSION: MirSNP could identify the putative miRNA-related SNPs from GWAS and eQTLs researches and provide the direction for subsequent functional researches.
  BMC Genomics 11/2012; 13(1):661. · 4.07 Impact Factor
• Article: No association of catechol-o-methyltransferase polymorphisms with schizophrenia in the han chinese population.

  Fuquan Zhang, Chenxing Liu, Yaguang Chen, Lifang Wang, Tianlan Lu, Hao Yan, Yanyan Ruan, Weihua Yue, Dai Zhang
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  ABSTRACT: Aims: Genetics play a major role in the etiology of schizophrenia (SZ). Catechol-O-methyltransferase (COMT) is one of the promising candidate genes for SZ. A nonsynonymous single-nucleotide polymorphism (SNP), rs4680, causing a Valine (Val) to Methionine (Met) substitution, has been widely studied in relation to psychiatric phenotypes, including SZ, but with conflicting results. We conducted a two-stage study to examine the association of COMT polymorphisms with SZ in the Han Chinese population. Results: Association analysis of nine SNPs in 768 patients and 1348 controls failed to detect any positive markers or haplotypes. Then, we tested rs4680 in a validation sample of 963 patients and 992 controls, and no significant association was observed, but the cases significantly deviated from Hardy-Weinberg equilibrium (p=5.7e-4). There was no association of rs4680 with SZ in the combined sample (n=4071, p=0.110, odds ratio=1.08). Conclusions: Our results do not support the association of COMT with SZ in the Han Chinese population.
  Genetic Testing and Molecular Biomarkers 09/2012; 16(9):1138-41. · 1.11 Impact Factor
• Article: Quetiapine prevents oligodendrocyte and myelin loss and promotes maturation of oligodendrocyte progenitors in the hippocampus of global cerebral ischemia mice.

  Xiaoying Bi, Yanbo Zhang, Bin Yan, Shaokuan Fang, Jue He, Dai Zhang, Zhijun Zhang, Jiming Kong, Qingrong Tan, Xin-Min Li
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  ABSTRACT: White matter impairment is a feature of vascular depression. The anti-psychotic quetiapine has been shown to enhance the therapeutic effects of anti-depressants on vascular depression, but the mechanism remains unknown. In this study, we found that 2 weeks of treatment with quetiapine prior to bilateral carotid artery occlusion and reperfusion, in an animal model of vascular depression, resulted in reduced myelin breakdown and oligodendrocyte loss compared to placebo-treated mice on post-operative day (POD) 7. For late stage of recovery (POD40), quetiapine treatment resulted in enhanced oligodendrocyte maturation relative to placebo. The results suggest that quetiapine is a potential intervention for oligodendrocyte damage and this may contribute to its anti-depressant effects through white matter protection in vascular depression.
  Journal of Neurochemistry 07/2012; 123(1):14-20. · 4.06 Impact Factor
• Article: Systematic association analysis of microRNA machinery genes with schizophrenia informs further study.

  Fuquan Zhang, Yaguang Chen, Chenxing Liu, Tianlan Lu, Hao Yan, Yanyan Ruan, Weihua Yue, Lifang Wang, Dai Zhang
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  ABSTRACT: microRNAs (miRNAs) play a vital role in development via the post-transcriptional regulation of most genes. Variation in the miRNA machinery pathway proteins which mediate the biogenesis, maturation, transportation, and functioning of miRNAs might be relevant to human traits. In this work, we explored the role of 59 miRNA machinery genes in schizophrenia (SZ). Association analysis of 967 single nucleotide polymorphisms within these genes detected that an intronic polymorphism of EIF4ENIF1, rs7289941, was significantly associated with SZ (P=4.10E-5). We failed to replicate this result in a validation sample comprising 1027 healthy controls and 1012 SZ cases, and the combined data yielded nominal significance (P=0.013). We conducted a gene-based association analysis using VEGAS and SKAT, and found seven associated genes in total, including EIF4ENIF1, PIWIL2, and DGCR8, but none survived correction for multiple testing. Taken together, our data do not provide strong support for the association of common variants within miRNA machinery genes with SZ in the Han Chinese population, but implicate several promising candidate genes for further research.
  Neuroscience Letters 05/2012; 520(1):47-50. · 2.11 Impact Factor
• Article: Quetiapine enhances oligodendrocyte regeneration and myelin repair after cuprizone-induced demyelination.

  Yanbo Zhang, Handi Zhang, Lingyan Wang, Wengao Jiang, Haiyun Xu, Lan Xiao, Xiaoying Bi, Junhui Wang, Shenghua Zhu, Ruiguo Zhang, Jue He, Qingrong Tan, Dai Zhang, Jiming Kong, Xin-Min Li
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  ABSTRACT: Myelin and oligodendrocyte dysfunctions have been consistently found in patients with schizophrenia. The effect of antipsychotics on myelin disturbances is unknown. The present study examined the effects of quetiapine on oligodendrocyte regeneration and myelin repair in a demyelination animal model. C57BL/6 mice were fed with cuprizone (0.2% w/w) for 12 weeks to induce chronic demyelination and oligodendrocyte degeneration, after which cuprizone was withdrawn to allow recovery. Quetiapine (10mg/kg/day) or vehicle (water) was administrated orally to mice for 0, 2, 3, or 4 weeks after cuprizone withdrawal. Locomotor activity and Y-maze tests were used to evaluate behavioral changes in the mice. Immunohistochemical staining was used to detect morphological and biological changes in the brains. Cuprizone administration for 12 weeks resulted in severe demyelination, locomotor hyperactivity, and working memory impairment in mice. Remyelination occurred when cuprizone was withdrawn. Quetiapine treatment during the recovery period significantly improved the spatial working memory and increased myelin restoration. Quetiapine treatment also enhanced the repopulation of mature oligodendrocytes in the demyelinated lesions, which was associated with down-regulation of transcription factor olig2 in the process of cell maturation. The results of this study demonstrated that quetiapine treatment during the recovery period improves spatial working memory and promotes oligodendrocyte development and remyelination. This study supports the role of oligodendrocyte dysfunction in memory deficits in a schizophrenia mouse model and suggests that quetiapine may target oligodendrocytes and improve cognitive function.
  Biological Psychiatry 05/2012; 138(1):8-17. · 8.28 Impact Factor
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  Available from: PubMed Central

  Article: Association between ghrelin gene (GHRL) polymorphisms and clinical response to atypical antipsychotic drugs in Han Chinese schizophrenia patients.

  Yongfeng Yang, Wenqiang Li, Jingyuan Zhao, Hongxing Zhang, Xueqin Song, Bo Xiao, Ge Yang, Chengdi Jiang, Dai Zhang, Weihua Yue, Luxian Lv
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  ABSTRACT: Ghrelin (GHRL) is a pivotal peptide regulator of food intake, energy balance, and body mass. Weight gain (WG) is a common side effect of the atypical antipsychotics (AAPs) used to treat schizophrenia (SZ). Ghrelin polymorphisms have been associated with pathogenic variations in plasma lipid concentrations, blood pressure, plasma glucose, and body mass index (BMI). However, it is unclear whether GHRL polymorphisms are associated with WG due to AAPs. Furthermore, there is no evidence of an association between GHRL polymorphisms and SZ or the therapeutic response to AAPs. We explored these potential associations by genotyping GHRL alleles in SZ patients and controls. We also examined the relation between these SNPs and changes in metabolic indices during AAP treatment in SZ subgroups distinguished by high or low therapeutic response. Four SNPs (Leu72Met, -501A/C, -604 G/A, and -1062 G > C) were genotyped in 634 schizophrenia patients and 606 control subjects. There were no significant differences in allele frequencies, genotype distributions, or the distributions of two SNP haplotypes between SZ patients and healthy controls (P > 0.05). There was also no significant difference in symptom reduction between genotypes after 8 weeks of AAP treatment as measured by positive and negative symptom scale scores (PANSS). However, the -604 G/A polymorphism was associated with a greater BMI increase in response to AAP administration in both APP responders and non-responders as distinguished by PANSS score reduction (P < 0.001). There were also significant differences in WG when the responder group was further subdivided according to the specific AAP prescribed (P < 0.05). These four GHRL gene SNPs were not associated with SZ in this Chinese Han population. The -604 G/A polymorphism was associated with significant BW and BMI increases during AAP treatment. Patients exhibiting higher WG showed greater improvements in positive and negative symptoms than patients exhibiting lower weight gain or weight loss.
  Behavioral and Brain Functions 02/2012; 8:11. · 2.13 Impact Factor
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  Available from: Hao Yan

  Article: Functional and anatomical connectivity abnormalities in cognitive division of anterior cingulate cortex in schizophrenia.

  Hao Yan, Lin Tian, Jun Yan, Wei Sun, Qi Liu, Yan-Bo Zhang, Xin-Ming Li, Yu-Feng Zang, Dai Zhang
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  ABSTRACT: Current pathophysiological theories of schizophrenia highlight the role of altered brain functional and anatomical connectivity. The cognitive division of anterior cingulate cortex (ACC-cd) is a commonly reported abnormal brain region in schizophrenia for its importance in cognitive control process. The aim of this study was to investigate the functional and anatomical connectivity of ACC-cd and its cognitive and clinical manifestation significance in schizophrenia by using the resting-state functional magnetic resonance imaging (fMRI) and the diffusion tensor imaging (DTI). Thirty-three medicated schizophrenics and 30 well-matched health controls were recruited. Region-of-interest (ROI)-based resting-state functional connectivity analysis and Tract-Based Spatial Statistics (TBSS) were performed on 30 patients and 30 controls, and 24 patients and 29 controls, respectively. The Pearson correlation was performed between the imaging measures and the Stroop performance and scores of the Positive and Negative Syndrome Scale (PANSS), respectively. Patients with schizophrenia showed significantly abnormal in the functional connectivity and its hemispheric asymmetry of the ACC-cd with multiple brain areas, e.g., decreased positive connectivity with the bilateral putamen and caudate, increased negative connectivity with the left posterior cingulated cortex (PCC), increased asymmetry of connectivity strength with the contralateral inferior frontal gyrus (IFG). The FA of the right anterior cingulum was significantly decreased in patients group (p = 0.014). The abnormal functional and structural connectivity of ACC-cd were correlated with Stroop performance and the severity of the symptoms in patients. Our results suggested that the abnormal connectivity of the ACC-cd might play a role in the cognitive impairment and clinical symptoms in schizophrenia.
  PLoS ONE 01/2012; 7(9):e45659. · 4.09 Impact Factor
• Article: Genome-wide association study identifies a susceptibility locus for schizophrenia in Han Chinese at 11p11.2.

  Wei-Hua Yue, Hai-Feng Wang, Liang-Dan Sun, Fu-Lei Tang, Zhong-Hua Liu, Hong-Xing Zhang, Wen-Qiang Li, Yan-Ling Zhang, Yang Zhang, Cui-Cui Ma, [......], Ling-Jiang Li, Xin Yu, Qi-Zhai Li, Xun Huang, Lu-Xian Lv, Tao Li, Guo-Ping Zhao, Wei Huang, Xue-Jun Zhang, Dai Zhang
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  ABSTRACT: To identify susceptibility loci for schizophrenia, we performed a two-stage genome-wide association study (GWAS) of schizophrenia in the Han Chinese population (GWAS: 746 individuals with schizophrenia and 1,599 healthy controls; validation: 4,027 individuals with schizophrenia and 5,603 healthy controls). We identified two susceptibility loci for schizophrenia at 6p21-p22.1 (rs1233710 in an intron of ZKSCAN4, P(combined) = 4.76 × 10(-11), odds ratio (OR) = 0.79; rs1635 in an exon of NKAPL, P(combined) = 6.91 × 10(-12), OR = 0.78; rs2142731 in an intron of PGBD1, P(combined) = 5.14 × 10(-10), OR = 0.79) and 11p11.2 (rs11038167 near the 5' UTR of TSPAN18, P(combined) = 1.09 × 10(-11), OR = 1.29; rs11038172, P(combined) = 7.21 × 10(-10), OR = 1.25; rs835784, P(combined) = 2.73 × 10(-11), OR = 1.27). These results add to previous evidence of susceptibility loci for schizophrenia at 6p21-p22.1 in the Han Chinese population. We found that NKAPL and ZKSCAN4 were expressed in postnatal day 0 (P0) mouse brain. These findings may lead to new insights into the pathogenesis of schizophrenia.
  Nature Genetics 12/2011; 43(12):1228-31. · 35.53 Impact Factor
• Article: Hyperforin promotes mitochondrial function and development of oligodendrocytes

  Yanlin Wang, Yanbo Zhang, Jue He, Handi Zhang, Lan Xiao, Adil Nazarali, Zhijun Zhang, Dai Zhang, Qingrong Tan, Jiming Kong, Xin-Min Li
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  ABSTRACT: J. Neurochem. (2011) 119, 555–568.AbstractSt. John’s wort has been found to be an effective and safe herbal treatment for depression in several clinical trials. However, the underlying mechanism of its therapeutic effects is unclear. Recent studies show that the loss and malfunction of oligodendrocytes are closely related to the neuropathological changes in depression, which can be reversed by antidepressant treatment. In this study, we evaluated the effects of hyperforin, a major active component of St. John’s wort, on the proliferation, development and mitochondrial function of oligodendrocytes. The study results revealed that hyperforin promotes maturation of oligodendrocytes and increases mitochondrial function without affecting proliferation of an oligodendrocyte progenitor cell line and neural stem/progenitor cells. Hyperforin also prevented mitochondrial toxin-induced cytotoxicity in an oligodendrocyte progenitor cell line. These findings suggest that hyperforin may stimulate the development and function of oligodendrocytes, which could be a mechanism of its effect in depression. Future in vitro and in vivo studies are required to further characterize the mechanisms of hyperforin.
  Journal of Neurochemistry 09/2011; 119(3):555 - 568. · 4.06 Impact Factor
• Article: No association of polymorphisms in the CDK5, NDEL1, and LIS1 with autism in Chinese Han population.

  Lifang Wang, Jun Li, Meixiang Jia, Weihua Yue, Yanyan Ruan, Tianlan Lu, Jishui Zhang, Jing Liu, Dai Zhang
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  ABSTRACT: Autism is a pervasive neurodevelopmental disorder. CDK5 (cyclin-dependent kinase 5) and its interacting molecules are involved in neurodevelopment. We performed a family-based association analysis between CDK5, NDEL1, and LIS1 polymorphisms and autism in a Chinese Han population. Our study did not detect a significant association. It indicated that common genetic variations in these genes might not play a role in the genetic predisposition to autism.
  Psychiatry Research 09/2011; 190(2-3):369-71. · 2.52 Impact Factor
• Article: To the editor: association of ZNF804A polymorphisms with schizophrenia and antipsychotic drug efficacy in a Chinese Han population.

  Bo Xiao, Wenqiang Li, Hongxing Zhang, Luxian Lv, Xueqin Song, Yongfeng Yang, Wei Li, Ge Yang, Chengdi Jiang, Jingyuan Zhao, Tianlan Lu, Dai Zhang, Weihua Yue
  Psychiatry Research 06/2011; 190(2-3):379-81. · 2.52 Impact Factor
• Article: Positive association of the human STON2 gene with schizophrenia.

  Zhilin Luan, Yanling Zhang, Tianlan Lu, Yan Ruan, Hongyan Zhang, Jun Yan, Lingzhi Li, Wei Sun, Lifang Wang, Weihua Yue, Dai Zhang
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  ABSTRACT: Synaptic hypothesis of schizophrenia suggests that alterations of synaptic transmission and neuronal connectivity might be core feature of schizophrenia. STON2 participates in synaptic vesicle protein recognition and neural endocytosis. To explore the association of STON2 with schizophrenia, 11 single nucleotide polymorphisms (SNPs) were examined in 768 Chinese Han schizophrenia cases and 1347 Chinese Han controls. The results showed that three SNPs had strong association with schizophrenia, two exonic SNPs (rs2241621: allelic P=0.0005; rs3813535: allelic P=0.0078) and one intronic SNP (rs9323698: allelic P=0.0019). When haplotype analysis performed, two linkage disequilibrium blocks showed significant differences in frequency between cases and controls. Notably, our data displays an over-transmitted functional haplotype C-C (Pro307-Ala851) in schizophrenia cases. Our results suggest STON2 may be a susceptibility gene for schizophrenia.
  Neuroreport 03/2011; 22(6):288-93. · 1.66 Impact Factor
• Article: Analysis of DNA copy number aberrations by multiple ligation-dependent probe amplification on 50 intestinal type gastric cancers.

  Dai Zhang, Zhenning Wang, Yang Luo, Yan Xu, Yanshan Liu, Wei Yang, Xue Zhang
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  ABSTRACT: The molecular genetic alterations leading to gastric malignancy are largely unknown. This study aimed to unravel the genomic DNA copy number aberrations (CNAs) profile during gastric tumorigenesis. In this study, we performed genomic profiling in a set of 50 intestinal type gastric carcinomas by a PCR-based relative quantification method, multiple ligation-dependent probe amplification (MLPA) with 112 cancer-related gene loci selected throughout each human chromosome as probes of MLPA assay. Numerous chromosomal DNA CNAs, including gains of 3p22, 4q25, 8q24, 11p13, and 20q13, and losses of 1p36 and 9p21, were identified by MLPA assay as recurrent DNA CNAs in gastric cancer. Moreover, we found the median numbers of gains, losses, and total CNAs were significantly higher in lymph node metastasis positive patients than in cases without metastasis. And gain of 11p13 and losses of 9p21.3, 11q13.3, 17q25.3, and 22q11.23 were associated with lymph node metastasis (P < 0.05). Finally, two major groups, including G1 + 2 with a large number of CNAs and G3 + 4 with a small number of CNAs, can be successfully distinguished by hierarchical cluster analysis. Our results proved MLPA is a reliable and efficient method to evaluate DNA copy number changes in gastric cancers.
  Journal of Surgical Oncology 02/2011; 103(2):124-32. · 2.10 Impact Factor