Dataset Information

Effect of rs1344706 in the ZNF804A gene on the brain network.

ABSTRACT: ZNF804A rs1344706 (A/C) was the first SNP that reached genome-wide significance for schizophrenia. Recent studies have linked rs1344706 to functional connectivity among specific brain regions. However, no study thus far has examined the role of this SNP in the entire functional connectome. In this study, we used degree centrality to test the role of rs1344706 in the whole-brain voxel-wise functional connectome during the resting state. 52 schizophrenia patients and 128 healthy controls were included in the final analysis. In our whole-brain analysis, we found a significant interaction effect of genotype × diagnosis at the precuneus (PCU) (cluster size = 52 voxels, peak voxel MNI coordinates: x = 9, y = - 69, z = 63, F = 32.57, FWE corrected P < 0.001). When we subdivided the degree centrality network according to anatomical distance, the whole-brain analysis also found a significant interaction effect of genotype × diagnosis at the PCU with the same peak in the short-range degree centrality network (cluster size = 72 voxels, F = 37.29, FWE corrected P < 0.001). No significant result was found in the long-range degree centrality network. Our results elucidated the contribution of rs1344706 to functional connectivity within the brain network, and may have important implications for our understanding of this risk gene's role in functional dysconnectivity in schizophrenia.

SUBMITTER: Chen X

PROVIDER: S-EPMC5842752 | biostudies-literature | 2018

REPOSITORIES: biostudies-literature

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Effect of rs1344706 in the <i>ZNF804A</i> gene on the brain network.

Chen Xiongying X Zhang Zhifang Z Zhang Qiumei Q Zhao Wan W Zhai Jinguo J Chen Min M Du Boqi B Deng Xiaoxiang X Ji Feng F Wang Chuanyue C Xiang Yu-Tao YT Wu Hongjie H Dong Qi Q Chen Chuansheng C Li Jun J

NeuroImage. Clinical 20171216

<i>ZNF804A</i> rs1344706 (A/C) was the first SNP that reached genome-wide significance for schizophrenia. Recent studies have linked rs1344706 to functional connectivity among specific brain regions. However, no study thus far has examined the role of this SNP in the entire functional connectome. In this study, we used degree centrality to test the role of rs1344706 in the whole-brain voxel-wise functional connectome during the resting state. 52 schizophrenia patients and 128 healthy controls we ...[more]

PMID: 29527501

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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.

Dataset Information

Effect of rs1344706 in the ZNF804A gene on the brain network.

Publications

Effect of rs1344706 in the <i>ZNF804A</i> gene on the brain network.

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