Spontaneous Regional Brain Activity in Healthy Individuals is Nonlinearly Modulated by the Interaction of ZNF804A rs1344706 and COMT rs4680 Polymorphisms

Cui, Lingling; Wang, Fei; Chang, Miao; Zhang, Yin; Fan, Guoguang; Song, Yumeng; Wei, Yange; Xu, Yixiao; Zhang, Yifan; Tang, Yanqing; Gong, Xiaohong

doi:10.1007/s12264-019-00357-w

Cited by 6 publications

(10 citation statements)

References 59 publications

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“…Besides, the distribution of the DC is more likely to be a U-shaped curve in these cortical regions and an inverted U-shaped curve in the putamen, according to the presumed dopamine signaling from high to low. The U-shaped and inverted U-shaped curves modulated by dopamine signaling have recently been reported in several studies 45,98,99 . For example, Zhao et al 98 reported networkdependent modulations of dopamine signaling on brain function, in which the intra-network functional connectivities of the brain "processing system" and "control system" were differently modulated by the COMT × DRD2 interaction effects.…”

Section: Discussionmentioning

confidence: 68%

Effects of COMT rs4680 and BDNF rs6265 polymorphisms on brain degree centrality in Han Chinese adults who lost their only child

Luo

Zhang

et al. 2020

Transl Psychiatry

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Losing one's only child is a major traumatic life event that may lead to posttraumatic stress disorder (PTSD); however, not all parents who experience this trauma develop PTSD. Genetic variants are associated with the risk of developing PTSD. Catechol-O-methyltransferase (COMT) rs4680 and brain-derived neurotrophic factor (BDNF) rs6265 are two most well-described single-nucleotide polymorphisms that relate to stress response; however, the neural mechanism underlying their effects on adults who lost an only child remains poorly understood. Two hundred and ten Han Chinese adults who had lost their only child (55 with PTSD and 155 without PTSD) were included in this imaging genetics study. Participants were divided into subgroups according to their COMT rs4680 and BDNF rs6265 genotypes. Degree Centrality (DC)-a resting-state fMRI index reflecting the brain network communication-was compared with a three-way (PTSD diagnosis, COMT, and BDNF polymorphisms) analysis of covariance. Diagnosis state had a significant effect on DC in bilateral inferior parietal lobules and right middle frontal gyrus (MFG), where PTSD adults showed weaker DC. BDNF × diagnosis interaction effect was found in the right MFG and hippocampus, and these two regions were reversely modulated. Also, there was a significant COMT × BDNF interaction effect in left cuneus, middle temporal gyrus, right inferior occipital gyrus, and bilateral putamen, independent of PTSD diagnosis. These findings suggest that the modulatory effect of BDNF polymorphism on the MFG and hippocampus may contribute to PTSD development in bereaved adults. Interactions of COMT × BDNF polymorphisms modulate some cortices and basal ganglia, irrespective of PTSD development.

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Section: Discussionmentioning

confidence: 68%

Effects of COMT rs4680 and BDNF rs6265 polymorphisms on brain degree centrality in Han Chinese adults who lost their only child

Luo

Zhang

et al. 2020

Transl Psychiatry

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“…Furthermore, we found that risk allele A was associated with neural activity only in the left anterior cingulate gyrus but not in rDLPFC, dorsomedial prefrontal cortex, left calcarine gyrus, and posterior cingulate cortex, which were reported in other studies. 18 , 19 , 29 These differences may be due to a higher statistical powerful in our meta-analysis. Thus, relatively less regions were found to be associated with risk allele A.…”

Section: Discussionmentioning

confidence: 92%

“… 18 In a neural activity research based on the amplitude of low-frequency fluctuation, the risk allele A exhibited a negative effect on the left calcarine gyrus. 19 …”

Section: Introductionmentioning

confidence: 99%

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

Xu¹,

He²,

Li³

et al. 2021

NDT

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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).

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“…The results indicated that: i) the main effect of disease factors revealed that the FA value of the right posterior radiocrown in the SZ group was significantly lower than ------------------------------------------------------------ that in the HC group; ii) the main effect of rs1344706 polymorphism in the ZNF804a gene revealed that the FA value of the right lower occipital east and right upper radiocrown were significantly lower; and iii) the interaction of the same gene polymorphism in the SZ group revealed that the FA value of the patient group was significantly lower than that in the control group, Compared with the AA control group, the FA value in the splenium of the corpus callosum, the body part of the corpus callosum part and the right cingulate tract in the gene carrier group was significantly decreased. The findings of Cui et al (16) suggest that ZNF804A affects the resting-state functional activation by interacting with COMT and may improve our understanding of the neurobiological effects of ZNF804A and its association with schizophrenia (16,37). The FA value of the SZ group was significantly lower than that of HC group.…”

Section: Discussionmentioning

confidence: 95%

“…It has also been revealed that the genetic defects and neurodevelopmental abnormalities of SZ were related to the dysfunction of glutamatergic neurons (15). The mutation of the ZNF804a gene in some SZ patients leads to the dysregulation of the glutamatergic synapse and nerve fiber, which leads to the abnormal development and function of the nerve fiber, and affects the development of brain white matter (16). In addition, it has been revealed that ZNF804a can regulate GABA energy transmission by pre-synaptic ErbB4 receptor (17).…”

Section: Introductionmentioning

confidence: 99%

rs1344706 polymorphism of zinc finger protein 804a (ZNF804a) gene related to the integrity of white matter fiber bundle in schizophrenics

et al. 2021

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Genetic factors play an important role in the pathogenesis of schizophrenia (SZ), and the zinc finger protein 804a (ZNF804a) gene has been considered to be a risk gene for schizophrenia. In the present study, the correlation between rs1344706 polymorphism of ZNF804a gene and the integrity of white matter in schizophrenic cases was explored. A total of 60 SZ patients and 100 healthy controls (HC) were included to undergo head MRI. According to the genotyping of rs1344706 in ZNF804a, the subjects in each group were divided into a normal allele and risk allele-carrying group. The imaging data were preprocessed by PANDA software, and thefractional anisotropy (FA) of each subject was calculated. With SPM8 software, age and years of education were considered as covariates, and diagnosis as well as genotype (AA, GG/AG) were considered as intergroup factors. Four groups of FA images were analyzed by two-factor analysis of variance. The FA value of the right posterior radiocrown in the patient group was lower than that in the control group, and the difference was statistically significant. The FA value of the right lower frontal occipital tract and the right upper radiocrown in the G allele carrier group was lower than that in the A allele homozygous group. There was detection of an interaction between the FA value of the splenium of corpus callosum, the body part of the corpus callosum and the right cingulate tract. In the present study, it was demonstrated that the rs1344706 GG/AG genotype of the ZNF804a gene locus in SZ patients suffered from abnormal structure in a specific region of the brain. This finding indicated that the rs1344706 single nucleotide polymorphism of the ZNF804a gene may affect the integrity of the white matter of the brain in SZ patients and may be involved in the pathophysiological mechanism of SZ.

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Spontaneous Regional Brain Activity in Healthy Individuals is Nonlinearly Modulated by the Interaction of ZNF804A rs1344706 and COMT rs4680 Polymorphisms

Cited by 6 publications

References 59 publications

Effects of COMT rs4680 and BDNF rs6265 polymorphisms on brain degree centrality in Han Chinese adults who lost their only child

Effects of COMT rs4680 and BDNF rs6265 polymorphisms on brain degree centrality in Han Chinese adults who lost their only child

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

rs1344706 polymorphism of zinc finger protein 804a (ZNF804a) gene related to the integrity of white matter fiber bundle in schizophrenics

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