Genome-wide association studies identified the single nucleotide polymorphism rs1344706 in ZNF804A as a common risk-variant for schizophrenia and bipolar disorder.
This study replicates the original reported association of ZNF804A with schizophrenia and suggests that there is a consistent link between the A allele of rs1344706, increased expression of ZNF804A and risk for schizophrenia.
Particularly rs1344706, initially surpassing the genome-wide significance level in an extended phenotype of schizophrenia and affective disorder, produced consistently negative results.
Our findings suggest that ZNF804A rs1344706 may aggravate the risk for schizophrenia by exerting its effects on cortical thickness, surface area, and cortical volume in these brain regions.
This finding might be consistent with a previously reported ZNF804A association in schizophrenia, in which patients carrying the schizophrenia-risk allele at rs1344706 showed a better performance in two memory tests.
Here, we studied rs1344706 and schizophrenia susceptibility in multiple Asian case-control samples (10 Chinese and 2 Japanese samples; N = 21,062), and the meta-analyses indicated non-significant association of rs1344706 with schizophrenia (P = 0.26), suggesting the same SNP identified in European samples is not predisposing risk in Asians.
Analysing the groups separately (at p < 0.001, uncorrected), variation in rs1344706 showed effects on brain structure within the schizophrenia patients in several areas including the left and right inferior temporal, right supramarginal/superior temporal, right and left inferior frontal, left frontopolar, right and left dorsolateral/ventrolateral prefrontal cortices, and the right thalamus, as well as effects within the healthy controls in left lateral temporal, right anterior insula and left orbitofrontal cortical areas.
Here, we review literature recently published on ZNF804A, and analyze critical concepts related to the biology of ZNF804A and the role of rs1344706 in schizophrenia and bipolar disorder.
In contrast, rs1344706 genotype had a significant effect on ZNF804A allelic expression in second-trimester fetal brain, with the schizophrenia risk (T) allele associated with reduced ZNF804A expression.
The meta-analysis provided evidence for association between rs1344706 that surpasses widely accepted benchmarks of significance by several orders of magnitude for both schizophrenia (P=2.5 × 10(-11), odds ratio (OR) 1.10, 95% confidence interval 1.07-1.14) and schizophrenia and bipolar disorder combined (P=4.1 × 10(-13), OR 1.11, 95% confidence interval 1.07-1.14).
We review the evidence to date for the association between schizophrenia and the original risk variant rs1344706 identified as well as additional common and rare variants at this locus.
Recently, the first common genetic variant associated on a genome-wide level with schizophrenia and possibly bipolar disorder was discovered in ZNF804A (rs1344706).
Further evidence for the association of genetic variants of ZNF804A with schizophrenia and a meta-analysis for genome-wide significance variant rs1344706.
The results of our meta-analysis were not able to confirm an association of rs1344706 A-allele with schizophrenia</span> (p = 0.10, odds ratio = 1.06, 95% confidence interval = 0.99-1.13).
The SNP rs1344706 was not associated with schizophrenia in either of the two Han Chinese groups, and this result was confirmed by meta-analyses in five Han Chinese samples.
Genetic imaging studies link the SZ risk variant rs1344706 on the ZNF804A gene to psychosis via alterations in functional brain connectivity during WM, but no work has looked at the effects of ZNF804A on WM with face-processing components.