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

  • Lingling Cui
  • Fei Wang
  • Miao Chang
  • Zhiyang Yin
  • Guoguang Fan
  • Yanzhuo Song
  • Yange Wei
  • Yixiao Xu
  • Yifan Zhang
  • Yanqing TangEmail author
  • Xiaohong GongEmail author
  • Ke XuEmail author
Original Article


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.


Zinc 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.

Supplementary material

12264_2019_357_MOESM1_ESM.pdf (294 kb)
Supplementary material 1 (PDF 294 kb)


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Copyright information

© Shanghai Institutes for Biological Sciences, CAS 2019

Authors and Affiliations

  • Lingling Cui
    • 1
    • 2
  • Fei Wang
    • 1
    • 3
    • 4
  • Miao Chang
    • 1
    • 4
  • Zhiyang Yin
    • 3
    • 4
  • Guoguang Fan
    • 1
  • Yanzhuo Song
    • 3
    • 4
  • Yange Wei
    • 3
    • 4
  • Yixiao Xu
    • 3
    • 4
  • Yifan Zhang
    • 3
    • 4
  • Yanqing Tang
    • 3
    • 4
    • 5
    Email author
  • Xiaohong Gong
    • 2
    Email author
  • Ke Xu
    • 1
    Email author
  1. 1.Department of RadiologyThe First Affiliated Hospital of China Medical UniversityShenyangChina
  2. 2.State Key Laboratory of Genetic Engineering and Ministry of Education Key Laboratory of Contemporary Anthropology, School of Life SciencesFudan UniversityShanghaiChina
  3. 3.Department of PsychiatryThe First Affiliated Hospital of China Medical UniversityShenyangChina
  4. 4.Brain Function Research SectionThe First Affiliated Hospital of China Medical UniversityShenyangChina
  5. 5.Department of GeriatricsThe First Affiliated Hospital of China Medical UniversityShenyangChina

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