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H Chang, X Xiao, M Li
ZNF804A (zinc-finger protein 804A) has been recognized as a schizophrenia risk gene across multiple world populations. Its intronic single-nucleotide polymorphism (SNP) rs1344706 is among one of the strongest susceptibility variants that have achieved genome-wide significance in genome-wide association studies (GWAS) for schizophrenia and has been widely and intensively studied. To elucidate the biological mechanisms underlying the genetic risk conferred by rs1344706, we retrospectively analyzed the progresses in brain gene expression quantitative trait loci (eQTL) analyses, ZNF804A-induced pathway alterations in neural cells and changes in synaptic phenotypes associated with ZNF804A expression...
March 14, 2017: Molecular Psychiatry
Chiara Fabbri, Concetta Crisafulli, Raffaella Calati, Diego Albani, Gianluigi Forloni, Marco Calabrò, Rosalba Martines, Siegfried Kasper, Joseph Zohar, Alzbeta Juven-Wetzler, Daniel Souery, Stuart Montgomery, Julien Mendlewicz, Alessandro Serretti
Genes belonging to neuroplasticity, monoamine, circadian rhythm, and transcription factor pathways were investigated as modulators of antidepressant efficacy. The present study aimed (1) to replicate previous findings in an independent sample with treatment-resistant depression (TRD), and (2) to perform a pathway analysis to investigate the possible molecular mechanisms involved. 220 patients with major depressive disorder who were non-responders to a previous antidepressant were treated with venlafaxine for 4-6 weeks and in case of non-response with escitalopram for 4-6 weeks...
March 4, 2017: European Archives of Psychiatry and Clinical Neuroscience
Shuquan Rao, Yao Yao, Joanne Ryan, Chunhui Jin, Yong Xu, Xinhe Huang, Jianxiu Guo, Yueqiang Wen, Canquan Mao, David Meyre, Fuquan Zhang
Rs1344706 in the the zinc finger protein 804A (ZNF804A) gene has been identified to be associated with schizophrenia and bipolar disorder (BD) in Europeans. However, whether rs1344706 is associated with schizophrenia in Chinese populations remains inconclusive; furthermore, the association between rs1344706 and BD in Chinese populations has been rarely explored. To explore the association between rs1344706 and schizophrenia/BD in Chinese populations, we genotyped rs1344706 among 1128 Chinese subjects (537 patients with BD and 591 controls) and found that rs1344706 showed marginal allelic association with BD (P = 0...
January 25, 2017: Scientific Reports
Qiang Xu, Yongqin Xiong, Congcong Yuan, Feng Liu, Fangshi Zhao, Junlin Shen, Wen Qin, Chunshui Yu
The biological function of ZNF804A rs1344706, the first genome-wide supported risk variant of schizophrenia, remains largely unknown. Based on the upregulating effect of ZNF804A on the expression of COMT, we hypothesize that ZNF804A may affect grey matter volume (GMV) by interacting with COMT. Voxel-based morphometry was applied to analyze the main and interaction effects of ZNF804A rs1344706 and COMT rs4680 on brain GMV in 274 healthy young human subjects. The GMV of the left dorsolateral prefrontal cortex (DLPFC) showed a significant COMT rs4680 × ZNF804A rs1344706 interaction, manifesting as an inverted U-shape modulation by the presumed dopamine signaling...
January 11, 2017: Brain Imaging and Behavior
X Pham, G Song, S Lao, L Goff, H Zhu, D Valle, D Avramopoulos
We previously reported a schizophrenia-associated polymorphic CT di-nucleotide repeat (DNR) at the 5'-untranslated repeat (UTR) of DPYSL2, which responds to mammalian target of Rapamycin (mTOR) signaling with allelic differences in reporter assays. Now using microarray analysis, we show that the DNR alleles interact differentially with specific proteins, including the mTOR-related protein HuD/ELAVL4. We confirm the differential binding to HuD and other known mTOR effectors by electrophoretic mobility shift assays...
November 1, 2016: Translational Psychiatry
E Mallas, F Carletti, C A Chaddock, S Shergill, J Woolley, M M Picchioni, C McDonald, T Toulopoulou, E Kravariti, S Kalidindi, E Bramon, R Murray, G J Barker, D P Prata
Genome-wide studies have identified allele A (adenine) of single nucleotide polymorphism (SNP) rs1006737 of the calcium-channel CACNA1C gene as a risk factor for both schizophrenia (SZ) and bipolar disorder (BD) as well as allele A for rs1344706 in the ZNF804A gene. These illnesses have also been associated with white matter abnormalities, reflected by reductions in fractional anisotropy (FA), measured using diffusion tensor imaging (DTI). We assessed the impact of the CACNA1C psychosis risk variant on FA in SZ, BD and health...
April 2017: Genes, Brain, and Behavior
Jianjun Ou, Ming Li, Xiao Xiao
OBJECTIVES: Genome-wide association studies (GWAS) followed by independent replications suggest that ZNF804A is a risk gene for schizophrenia (SCZ), considering the substantial genetic overlap between SCZ and major mood disorders (e.g., bipolar disorder (BPD) and major depressive disorder (MDD)). METHODS: We collected the data of two ZNF804A single-nucleotide polymorphisms (SNPs rs1344706 and rs7597593) from European and Asian populations to perform systematic meta-analyses with major mood disorders in a total of 65,240 subjects...
November 21, 2016: World Journal of Biological Psychiatry
Porcelli Stefano, Crisafulli Concetta, Donato Luigi, Calabrò Marco, Politis Antonis, Liappas Ioannis, Albani Diego, Atti Anna Rita, Salfi Raffaele, Raimondi Ilaria, Forloni Gianluigi, Papadimitriou George N, De Ronchi Diana, Serretti Alessandro
INTRODUCTION: With the increase of the population's average age, Alzheimer's disease (AD) is becoming one of the most disabling diseases worldwide. Recently, neurodevelopment processes have been involved in the AD etiopathogenesis. Genetic studies in this field could contribute to our knowledge and suggest new molecular targets for possible treatments. METHODS: Our primary aim was to investigate the associations among single nucleotide polymorphisms (SNPs) within neurodevelopment related genes (BDNF, ST8SIA2, C15orf32, NCAPG2, ESYT2, WDR60, LOC154822, VIPR2, GSK3B, NR1I2, ZNF804A, SP4) and AD...
November 15, 2016: Journal of the Neurological Sciences
Xiao Xiao, Xiong-Jian Luo, Hong Chang, Zichao Liu, Ming Li
Schizophrenia is a severe and highly heritable neuropsychiatric disorder. Recent genetic analyses including genome-wide association studies (GWAS) have implicated multiple genome-wide significant variants for schizophrenia among European populations. However, many of these risk variants were not largely validated in other populations of different ancestry such as Asians. To validate whether these European GWAS significant loci are associated with schizophrenia in Asian populations, we conducted a systematic literature search and meta-analyses on 19 single nucleotide polymorphisms (SNPs) in Asian populations by combining all available case-control and family-based samples, including up to 30,000 individuals...
June 18, 2016: Molecular Neurobiology
Peng He, Lin Sun, Dan Zhu, Hong Zhang, Liang Zhang, Yujie Guo, Siwen Liu, Jingjing Zhou, Xiaoyan Xu, Peng Xie
Endogenous bornavirus-like nucleoprotein elements (EBLNs) have been discovered in the genomes of various animals including humans, whose functions have been seldom studied. To explore the biological functions of human EBLNs, we constructed a lentiviral vector expressing a short-hairpin RNA against human EBLN1, which successfully inhibited EBLN1 expression by above 80% in infected human oligodendroglia cells (OL cells). We found that EBLN1 silencing suppressed cell proliferation, induced G2/M phase arrest, and promoted apoptosis in OL cells...
March 24, 2016: International Journal of Molecular Sciences
Emma-Jane Mallas, Francesco Carletti, Christopher A Chaddock, James Woolley, Marco M Picchioni, Sukhwinder S Shergill, Fergus Kane, Matthew P G Allin, Gareth J Barker, Diana P Prata
Background. Schizophrenia (SZ) and bipolar disorder (BD) have both been associated with reduced microstructural white matter integrity using, as a proxy, fractional anisotropy (FA) detected using diffusion tensor imaging (DTI). Genetic susceptibility for both illnesses has also been positively correlated in recent genome-wide association studies with allele A (adenine) of single nucleotide polymorphism (SNP) rs1344706 of the ZNF804A gene. However, little is known about how the genomic linkage disequilibrium region tagged by this SNP impacts on the brain to increase risk for psychosis...
2016: PeerJ
Jun Wang, Shuidi Zhao, Yin Yao Shugart, Zhenhe Zhou, Chunhui Jin, Jianmin Yuan, Guoqiang Wang, Dong Wang, Zaohuo Cheng, Fuquan Zhang
Previous studies indicated that the single nucleotide polymorphism (SNP) rs1344706 within the gene ZNF804A was a promising risk variant for schizophrenia in European populations. However, existing results are inconsistent in Han Chinese. Hoping to validate the association of rs1344706 with schizophrenia susceptibility in Han Chinese, we conducted a case-control study in 1284 cases and 990 healthy controls from Jiangsu Province, China. We did not detect any significant between-group difference (all P>0.05) in either allele or genotype frequency under any genetic model between cases and controls...
April 8, 2016: Neuroscience Letters
Liang Huang, Kazutaka Ohi, Hong Chang, Hao Yu, Lichuan Wu, Weihua Yue, Dai Zhang, Lei Gao, Ming Li
Common variants in ZNF804A increased the risk of schizophrenia (and bipolar disorder), with low effect sizes in Europeans, which is in line with the polygenic nature of the illnesses, and implies that genetic analyses in small samples may not be sufficient to detect stable results. This notion is supported by the inconsistent replications of ZNF804A variations among individual small Asian samples, indicating the absence of definitive conclusions in this population. We collected psychiatric phenotypic and genetic data from Asian genome-wide association (GWA) and individual replication studies, which include up to 13,452 cases, 17,826 healthy controls, and 680 families, that is, the largest-scale study on ZNF804A in Asian populations to date...
April 2016: American Journal of Medical Genetics. Part B, Neuropsychiatric Genetics
Zhifang Zhang, Xiongying Chen, Ping Yu, Qiumei Zhang, Xiaochen Sun, Huang Gu, Hao Zhang, Jinguo Zhai, Min Chen, Boqi Du, Xiaoxiang Deng, Feng Ji, Chuanyue Wang, Yutao Xiang, Dawei Li, Hongjie Wu, Jun Li, Qi Dong, Chuansheng Chen
ZNF804A is one of the most promising candidate genes for schizophrenia. Previous fMRI studies have repeatedly shown an association between SNP rs1344706 in this gene and the functional connectivity from the right dorsolateral prefrontal cortex (rDLPFC) to the left hippocampal formation (lHF) during the N-back task. However, the rDLPFC-lHF functional connectivity included several subconnections and it is not known whether rs1344706 plays the same role in these subconnections. This study addressed that question using both fMRI and DTI data of 87 subjects...
January 2016: Schizophrenia Research
D B Hancock, J L Levy, N C Gaddis, C Glasheen, N L Saccone, G P Page, L J Bierut, A H Kral, E O Johnson
Heroin addiction is heritable, but few specific genetic variants have been reproducibly associated with this disease. The zinc finger protein 804A (ZNF804A) gene is a biologically plausible susceptibility gene for heroin addiction, given its function as a transcription factor in human brain. Novel associations of two common ZNF804A single nucleotide polymorphisms (SNPs), rs7597593 and rs1344706, with heroin addiction have been reported in Han Chinese. Both SNPs have also been implicated for regulating ZNF804A expression in human brain, including the addiction-relevant dorsolateral prefrontal cortex...
November 2015: Genes, Brain, and Behavior
Eric H Chang, Anne Kirtley, Toni-Shay S Chandon, Philip Borger, Sehba Husain-Krautter, Valerie Vingtdeux, Anil K Malhotra
The zinc finger protein ZNF804A rs1344706 variant is a replicated genome-wide significant risk variant for schizophrenia and bipolar disorder. While its association with altered brain structure and cognition in patients and healthy risk allele carriers is well documented, the characteristics and function of the gene in the brain remains poorly understood. Here, we used in situ hybridization to determine mRNA expression levels of the ZNF804A rodent homologue, Zfp804a, across multiple postnatal neurodevelopmental time points in the rat brain...
October 2015: Schizophrenia Research
Katja Hvid Hinna, Karen Rich, Åsa Fex-Svenningsen, Eirikur Benedikz
A single nucleotide polymorphism in the ZNF804A gene, rs1344706, is associated with schizophrenia. The polymorphism has been suggested to alter fetal expression of ZNF804A. It has also been reported to be associated with altered cortical functioning and neural connectivity in the brain. Since developmental mechanisms are suggested in the pathophysiology for schizophrenia, expression of Zfp804A, the rat homolog of ZNF804A, was investigated in the developing rat brain. We found that expression of Zfp804A in most brain regions is developmentally regulated and peaks around birth, where after it decreases towards adult levels...
2015: PloS One
Chen Zhang, Zuowei Wang, Wu Hong, Zhiguo Wu, Daihui Peng, Yiru Fang
Genetic variation in the gene encoding zinc finger protein 804A gene (ZNF804A) has been identified to be associated with bipolar disorder in genome-wide association studies, while little is known regarding their association in Asian populations. In this study, we aimed to examine whether ZNF804A may confer susceptibility to BD in Han Chinese. We measured the mRNA expression level of ZNF804A in patients with BD and controls. Two functional variants (rs1344706 and rs359895) in ZNF804A were genotyped among 1508 individuals with or without BD...
July 2016: Molecular Neurobiology
Qinling Wei, Meng Li, Zhuang Kang, Leijun Li, Feici Diao, Ruibin Zhang, Junjing Wang, Liangrong Zheng, Xue Wen, Jinbei Zhang, Jingping Zhao, Ruiwang Huang
The effects of ZNF804A rs1344706, a prominent susceptibility gene for schizophrenia, on gray matter (GM) structure in unmedicated schizophrenia (SZ) patients are still unknown, although several previous studies investigated the effects in medicated SZ patients and healthy controls (HC). Analyzing cortical thickness, surface area, and GM volume simultaneously may provide a more precise and complete picture of the effects. We genotyped 59 unmedicated first episode SZ patients and 60 healthy controls for the ZNF804A single nucleotide polymorphism (SNP) rs1344706, and examined between-group differences in cortical thickness, surface area, and cortical volume using a full-factorial 2 × 2 analysis of variance (ANOVA)...
June 2015: American Journal of Medical Genetics. Part B, Neuropsychiatric Genetics
Jian Chen, Mingyan Lin, Anastasia Hrabovsky, Erika Pedrosa, Jason Dean, Swati Jain, Deyou Zheng, Herbert M Lachman
ZNF804A (Zinc Finger Protein 804A) has been identified as a candidate gene for schizophrenia (SZ), autism spectrum disorders (ASD), and bipolar disorder (BD) in replicated genome wide association studies (GWAS) and by copy number variation (CNV) analysis. Although its function has not been well-characterized, ZNF804A contains a C2H2-type zinc-finger domain, suggesting that it has DNA binding properties, and consequently, a role in regulating gene expression. To further explore the role of ZNF804A on gene expression and its downstream targets, we used a gene knockdown (KD) approach to reduce its expression in neural progenitor cells (NPCs) derived from induced pluripotent stem cells (iPSCs)...
2015: PloS One
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