Is the conserved mammalian region of ZNF804A locus associated with schizophrenia? A population-based genetics analysis

Zhang, Rui; Valenzuela, Robert K.; Lu, Shemin; Li, Meng; Guo, Tingwei; Kang, Wan-Hu; Ma, Jie

doi:10.1016/j.schres.2011.09.012

Cited by 14 publications

(16 citation statements)

References 33 publications

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“…4 Subsequent studies focused on ZNF804A strongly supported association with SZ. 5, 6, 7, 8, 9, 10, 11 ZNF804A is expressed in the brain, and the risk allele of rs1344706 has been associated with decreased mRNA expression during fetal brain development. 80 Knockdown of ZNF804A in neural progenitor cells changes expression of genes pertaining to neuronal outgrowth and migration, synapse formation, and cell adhesion, all of which have been implicated in the pathophysiology of SZ.…”

Section: Discussionmentioning

confidence: 99%

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Analysis of schizophrenia-related genes and electrophysiological measures reveals ZNF804A association with amplitude of P300b elicited by novel sounds

Bergen

Mesholam-Gately

et al. 2014

Transl Psychiatry

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Several genes have recently been identified as risk factors for schizophrenia (SZ) by genome-wide association studies (GWAS), including ZNF804A which is thought to function in transcriptional regulation. However, the downstream pathophysiological changes that these genes confer remain to be elucidated. In 143 subjects (68 clinical high risk, first episode or chronic cases; 75 controls), we examined the association between 21 genetic markers previously identified by SZ GWAS or associated with putative intermediate phenotypes of SZ against three event-related potential (ERP) measures: mismatch negativity (MMN), amplitude of P300 during an auditory oddball task, and P300 amplitude during an auditory novelty oddball task. Controlling for age and sex, significant genetic association surpassing Bonferroni correction was detected between ZNF804A marker rs1344706 and P300 amplitude elicited by novel sounds (beta=4.38, P=1.03 × 10−4), which is thought to index orienting of attention to unexpected, salient stimuli. Subsequent analyses revealed that the association was driven by the control subjects (beta=6.35, P=9.08 × 10−5), and that the risk allele was correlated with higher novel P300b amplitude, in contrast to the significantly lower amplitude observed in cases compared to controls. Novel P300b amplitude was significantly correlated with a neurocognitive measure of auditory attention under interference conditions, suggesting a relationship between novel P300b amplitude and higher-order attentional processes. Our results suggest pleiotropic effects of ZNF804A on risk for SZ and neural mechanisms that are indexed by the novel P300b ERP component.

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Section: Discussionmentioning

confidence: 99%

“…ZNF804A was initially implicated in risk of SZ and psychosis by a GWAS, and subsequently replicated by several targeted association studies. 4, 5, 6, 7, 8, 9, 10 A report of stronger association in SZ cases with higher IQ suggests that variation in ZNF804A may confer risk of a disease subtype with relatively preserved cognition. 11 …”

Section: Introductionmentioning

confidence: 99%

Analysis of schizophrenia-related genes and electrophysiological measures reveals ZNF804A association with amplitude of P300b elicited by novel sounds

Bergen

Mesholam-Gately

et al. 2014

Transl Psychiatry

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“…Dwyer and coworkers found no evidence that rare coding variants in ZNF804A conferred risk for schizophrenia . Zhang et al found no significant difference in the allele distributions of rs4666998 and rs56280129 among controls and schizophrenia patients, but the T-allele frequency at rs13423388 was significantly different between cases and controls (Zhang et al, 2011b). Overt differences were found for rs1366842 and rs4667000 between cases and controls with schizophrenia in Han Chinese, but no differences were found for several other loci (rs61739290, rs61739288, rs3731834; Li et al, 2011).…”

Section: Genetic Associationmentioning

confidence: 98%

“…The haplotype analysis of rs4666998-rs13423388-rs56281029 showed significant associations with schizophrenia. Furthermore, they performed a four-SNP haplotype (rs4666998-rs13423388-rs56281029-rs1344706) analysis and found that the G-C-C-G haplotype was associated with schizophrenia (Zhang et al, 2011b).…”

Section: Copy Number Variants and Haplotype Variants In Znf804amentioning

confidence: 99%

Association between variants of zinc finger genes and psychiatric disorders: Systematic review and meta-analysis

Sun

Liang

et al. 2015

Schizophrenia Research

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“…The first gene to reach genome-wide significance for psychosis was ZNF804a when SNP rs1344706 was significantly associated when schizophrenia and bipolar disorder diagnoses are combined [3]. Several follow up GWAS studies have replicated the association of rs1344706 with SZ in different populations [4], [5], [6], and several other SNPs near the ZNF804a locus have a significant association with SZ [7], [8].…”

Section: Introductionmentioning

confidence: 99%

ZNF804a Regulates Expression of the Schizophrenia-Associated Genes PRSS16, COMT, PDE4B, and DRD2

Girgenti

LoTurco²,

Maher³

2012

PLoS ONE

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ZNF804a was identified by a genome-wide association study (GWAS) in which a single nucleotide polymorphism (SNP rs1344706) in ZNF804a reached genome-wide statistical significance for association with a combined diagnosis of schizophrenia (SZ) and bipolar disorder. Although the molecular function of ZNF804a is unknown, the amino acid sequence is predicted to contain a C2H2-type zinc-finger domain and suggests ZNF804a plays a role in DNA binding and transcription. Here, we confirm that ZNF804a directly contributes to transcriptional control by regulating the expression of several SZ associated genes and directly interacts with chromatin proximal to the promoter regions of PRSS16 and COMT, the two genes we find upregulated by ZNF804a. Using immunochemistry we establish that ZNF804a is localized to the nucleus of rat neural progenitor cells in culture and in vivo. We demonstrate that expression of ZNF804a results in a significant increase in transcript levels of PRSS16 and COMT, relative to GFP transfected controls, and a statistically significant decrease in transcript levels of PDE4B and DRD2. Furthermore, we show using chromatin immunoprecipitation assays (ChIP) that both epitope-tagged and endogenous ZNF804a directly interacts with the promoter regions of PRSS16 and COMT, suggesting a direct upregulation of transcription by ZNF804a on the expression of these genes. These results are the first to confirm that ZNF804a regulates transcription levels of four SZ associated genes, and binds to chromatin proximal to promoters of two SZ genes. These results suggest a model where ZNF804a may modulate a transcriptional network of SZ associated genes.

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Is the conserved mammalian region of ZNF804A locus associated with schizophrenia? A population-based genetics analysis

Cited by 14 publications

References 33 publications

Analysis of schizophrenia-related genes and electrophysiological measures reveals ZNF804A association with amplitude of P300b elicited by novel sounds

Analysis of schizophrenia-related genes and electrophysiological measures reveals ZNF804A association with amplitude of P300b elicited by novel sounds

Association between variants of zinc finger genes and psychiatric disorders: Systematic review and meta-analysis

ZNF804a Regulates Expression of the Schizophrenia-Associated Genes PRSS16, COMT, PDE4B, and DRD2

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