Spontaneous Regional Brain Activity in Healthy Individuals is Nonlinearly Modulated by the Interaction of ZNF804A rs1344706 and COMT rs4680 Polymorphisms
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 Geriatrics, The First Affiliated Hospital of China Medical University, Shenyang 110001, China
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 ZNF804Aupregulates 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 ZNF804Ars1344706 × 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
Zinc finger protein 804A; Catechol-O-methyltransferase; Amplitudes of low-frequency fluctuations; fMRI
