Association Between rs1344706 of ZNF804A and Schizophrenia: A Meta-Analysis

Abstract

Schizophrenia is one of the most serious mental diseases found in humans. Previous studies indicated that the single nucleotide polymorphism (SNP) rs1344706 in the gene ZNF804A encoding zinc finger protein 804A was associated with schizophrenia in Caucasian population but not in Chinese Han population. However, current results are conflicting in Asian population. In the present study, a meta-analysis was performed to revisit the association between rs1344706 and the risk of schizophrenia in Asian, Caucasian and other populations. Electronic search of PubMed database identified 25 case–control studies with available genotype frequencies of rs1344706 for the meta-analysis, involving a total of 15,788 cases and 22,654 controls. A pooled odds ratio (OR) with 95% confidence interval (CI) was used to assess the association. The current meta-analysis showed an association between rs1344706 and schizophrenia in Caucasian populations (P = 0.028, OR = 1.138, 95% CI: 1.014–1.278; P = 0.004 for heterogeneity) and Asian populations (P = 0.008, OR = 1.092, 95% CI: 1.023–1.165; P = 0.001 for heterogeneity), but not in other populations (P = 0.286, OR = 1.209, 95% CI: 0.853–1.714, P = 0.120 for heterogeneity). Egger’s test (P > 0.05) and Begg’s test (P > 0.05) are both suggestive of the lack of publication bias for the included studies. Thus, the absence of association in other populations suggests a genetic heterogeneity in the susceptibility of schizophrenia and demonstrates the difficulties in replicating genome-wide association study findings regarding schizophrenia across different ethnic populations. To validate the association between rs1344706 and schizophrenia, further studies with larger participant populations worldwide are needed.

The impact of CACNA1C gene, and its epistasis with ZNF804A, on white matter microstructure in health, schizophrenia and bipolar disorder1

“…gene (Ferreira et al 2008;Green et al 2010;Guan et al 2014;He et al 2014;Jiang et al 2015;Nyegaard et al 2010;Sklar et al 2008;Zheng et al 2014) and allele A of the rs1344706 SNP of the ZNF804A gene (Donohoe et al 2010;Sun et al 2015;Zhang et al 2015;Zhu et al 2014). The latter variant has been associated with white matter (WM) microstructural abnormalities as we report elsewhere (Mallas et al 2016).…”

“…Genome‐wide association studies (GWAS) have identified two genetic variants conferring, so far the most reproducible, risk for both SZ and BD: allele A of the single nucleotide polymorphism (SNP) labelled rs1006737 of the CACNA1C gene (Ferreira et al ; Green et al ; Guan et al ; He et al ; Jiang et al ; Nyegaard et al ; Sklar et al ; Zheng et al ) and allele A of the rs1344706 SNP of the ZNF804A gene (Donohoe et al ; Sun et al ; Zhang et al ; Zhu et al ). The latter variant has been associated with white matter (WM) microstructural abnormalities as we report elsewhere (Mallas et al ).…”

Genetic Consideration of Schizotypal Traits: A Review

“…They are involved in multiple functions, including transcriptional activation, protein folding, RNA packaging, lipid binding, and DNA recognition (Laity et al, 2001). Recently, focus has been given to specific SNPs of ZNF804A (e.g., rs1344706, rs4667001, and rs728534) with a meta-analysis by Zhu et al (2014) showing an association with schizophrenia risk in both Asian and Caucasian populations. When investigating these SNPs in reference to schizotypy, we see mixed results with some studies finding a significant association with schizotypy (Yasuda et al, 2011; Stefanis et al, 2013) and others not (Leach et al, 2013).…”

Analyzing a single nucleotide polymorphism in schizophrenia: a meta-analysis approach

“…To this end, meta-analysis tests are performed to revalidate existing hypotheses using newer GWAS datasets. The association of this SNP has been inspected by four previous meta-analyses, 10 , 11 , 32 , 33 with the first study consisting of 12 studies from the Chinese population and stating no association and the second study consisting of 13 studies from the Asian population and stating the presence of association. The third meta-analysis consisted of 30 studies, which included Asians, Caucasians and Americans.…”

“…In addition, performing further analysis, they detected that the SNP rs359895 has an association with schizophrenia in the Chinese population. Zhu et al 11 performed a meta-analysis containing 13 Chinese samples, 10 Caucasian samples and two samples from other populations. Stratified and combined analysis in the three different groups showed association of SNP rs1344706 with schizophrenia.…”