Spontaneous Regional Brain Activity in Healthy Individuals is Nonlinearly Modulated by the Interaction of ZNF804A rs1344706 and COMT rs4680 Polymorphisms
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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.
KeywordsZinc finger protein 804A Catechol-O-methyltransferase Amplitudes of low-frequency fluctuations fMRI
This work was supported by the National Basic Research Development Program of China (2016YFC0906400, 2016YFC1306900 and 2016YFC0904300), the National Natural Science Foundation of China (81571311 and 81571331), the National Science Fund for Distinguished Young Scholars of China (81725005), the National High Tech Development Project (863 Project) of China (2015AA020513), the Science and Technology Project of Liaoning Province, China (2015225018), and the Educational Foundation (Pandeng Scholarship) of Liaoning Province, China. We are grateful for the support of Department of Radiology and Psychiatry, First Affiliated Hospital of China Medical University. We thank all the participants for their cooperation.
Conflicts of interest
The authors have no conflicts of interest to declare.
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