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Neurosci Bull. 2019 Mar 9. doi: 10.1007/s12264-019-00357-w. [Epub ahead of print]

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

Cui L1,2, Wang F1,3,4, Chang M1,4, Yin Z3,4, Fan G1, Song Y3,4, Wei Y3,4, Xu Y3,4, Zhang Y3,4, Tang Y5,6,7, Gong X8, Xu K9.

Author information

1
Department of Radiology, The First Affiliated Hospital of China Medical University, Shenyang, 110001, China.
2
State Key Laboratory of Genetic Engineering and Ministry of Education Key Laboratory of Contemporary Anthropology, School of Life Sciences, Fudan University, Shanghai, 200433, China.
3
Department of Psychiatry, The First Affiliated Hospital of China Medical University, Shenyang, 110001, China.
4
Brain Function Research Section, The First Affiliated Hospital of China Medical University, Shenyang, 110001, China.
5
Department of Psychiatry, The First Affiliated Hospital of China Medical University, Shenyang, 110001, China. yanqingtang@163.com.
6
Brain Function Research Section, The First Affiliated Hospital of China Medical University, Shenyang, 110001, China. yanqingtang@163.com.
7
Department of Geriatrics, The First Affiliated Hospital of China Medical University, Shenyang, 110001, China. yanqingtang@163.com.
8
State Key Laboratory of Genetic Engineering and Ministry of Education Key Laboratory of Contemporary Anthropology, School of Life Sciences, Fudan University, Shanghai, 200433, China. gongxh@fudan.edu.cn.
9
Department of Radiology, The First Affiliated Hospital of China Medical University, Shenyang, 110001, China. kxu@cmu.edu.cn.

Abstract

ZNF804A rs1344706 has been identified as one of the risk genes for schizophrenia. However, the neural mechanisms underlying this association are unknown. Given that ZNF804A upregulates the expression of COMT, we hypothesized that ZNF804A may influence brain activity by interacting with COMT. Here, we genotyped ZNF804A rs1344706 and COMT rs4680 in 218 healthy Chinese participants. Amplitudes of low-frequency fluctuations (ALFFs) were applied to analyze the main and interaction effects of ZNF804A rs1344706 and COMT rs4680. The ALFFs of the bilateral dorsolateral prefrontal cortex showed a significant ZNF804A rs1344706 × COMT rs4680 interaction, manifesting as a U-shaped modulation, presumably by dopamine signaling. Significant main effects were also found. These findings 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.

KEYWORDS:

Amplitudes of low-frequency fluctuations; Catechol-O-methyltransferase; Zinc finger protein 804A; fMRI

PMID:
30852803
DOI:
10.1007/s12264-019-00357-w

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