Dataset Information

Association Between ZNF804A Gene rs1344706 Polymorphism and Brain Functions in Healthy Individuals: A Systematic Review and Voxel-Based Meta-Analysis.

ABSTRACT:

Objective

Zinc finger protein 804A (ZNF804A) protein participates in embryonic neural repair and development. The single nucleotide polymorphism rs1344706 in ZNF804A gene is closely related to functional abnormalities of the human brain. However, these results are inconsistent. This association was verified by meta-analysis in this study.

Methods

Fifteen studies on functional magnetic resonance imaging involving 1710 healthy individuals were included in the systematic review and meta-analysis used by Anisotropic Effect-Size Signed Differential Mapping software.

Results

Functional connectivity of the right dorsolateral prefrontal cortex (rDLPFC)-left hippocampus in the rs1344706 risk allele carrier was significantly increased (z = 2.066, p < 0.001), while those in the rDLPFC-left middle frontal gyrus (z = -1.420, p < 0.001) and rDLPFC-right middle frontal gyrus (z = -1.298, p < 0.001) were significantly decreased. Neural activity of the left anterior cingulate gyrus in the rs1344706 risk allele carrier was significantly decreased (z = -2.525, p < 0.001). Sensitivity analysis was almost stable, and no publication bias was found.

Conclusion

The changes in brain function have a clear correlation with ZNF804A gene in healthy individuals, which indicate the contribution of genetic variants on brain dysfunction.

Registration number

This meta-analysis is registered in PROSPERO (No. CRD42016051331).

SUBMITTER: Yang L

PROVIDER: S-EPMC8449690 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:Abstract Background: Following both meta-analysis and extensive resequencing, the single-nucleotide polymorphism of allele A, rs1344706, located in intron 2 of the zinc-finger protein gene ZNF804A, continues to be the common variant most strongly associated with schizophrenia risk (P = 1.1_10–13). ZNF804a is highly expressed in adult brain and functional effects on both protein expression, and altered DNA–protein interaction have been reported. In addition, the ZNF804A rs1344706 A allele has recently been reported to be associated with worse clinical outcome. We were interested in examining whether another proxy for worse clinical outcome, the Positive and Negative Syndrome Scale (PANSS) excitement factor, is associated with a ZNF804a genotype. We hypothesized that a single-nucleotide polymorphism in ZNF804a could be associated with impulsivity. The aim of this study was to assess the association of a single-nucleotide polymorphism rs1344706 with the PANSS excitement factor. Methods: We tested the effect of rs1344706 (A/C) genotype in 133 individuals with DSM-5 chronic schizophrenia using the PANSS. Scores on the PANSS excitement factor were compared between individuals who expressed allele A and those who expressed allele C (individuals with the heterogeneous allele A/C were combined to the C group). General Linear Model (GLM) was used to analyze the differences between groups for the PANSS Excitement Factor (assessed by the summation of: excitement, hostility, uncooperativeness, and poor impulse control). Results: A total of 133 subjects were sampled for ZNF804; however, PANSS data were available for 122 subjects. Of the 122, 68.85% (n = 84) of subjects presented with allele A and 31.15% (n = 38) with allele C. In all, 67.85% (n = 57) of the individuals with allele A were African Americans, and 28.95% (n = 11) of individuals with allele C were African Americans, and 39.47% (n = 15) were Hispanics. The PANSS total score for the entire sample was 72.64 (SD = 9.33). PANSS excitement factor scores ranged from 4 to 15 in group A and 4 to 14 in group C. GLM analysis showed a significant difference in ZNF804, F(1, 121) = 5.595, P = .020, between individuals with allele A compared to those with allele C. The mean excitement factor score for allele A was lower (mean = 7.762, SE = 0.273) than for allele C group (mean = 8.921, SE = 0.427). Conclusion: While the risk “A” allele at rs1344706 has been associated with altered functional brain connectivity and represents a risk factor for psychosis, our results shows an association of the “C” allele at rs1344706 with impulsivity in chronic schizophrenia patients. The difference in our findings when compared to previous reports may have to do with the differing ethnic distribution of our population, which is predominantly African American. This finding could be of nosological value for biological subtyping across the spectrum of schizophrenia, although important limitations should be noted such as small sample size and lack of ethnic diversity of our population.