Brain Imaging and Behavior

, Volume 12, Issue 1, pp 13–19 | Cite as

ZNF804A rs1344706 interacts with COMT rs4680 to affect prefrontal volume in healthy adults

  • Qiang Xu
  • Yongqin Xiong
  • Congcong Yuan
  • Feng Liu
  • Fangshi Zhao
  • Junlin Shen
  • Wen Qin
  • Chunshui Yu
Original Research


The biological function of ZNF804A rs1344706, the first genome-wide supported risk variant of schizophrenia, remains largely unknown. Based on the upregulating effect of ZNF804A on the expression of COMT, we hypothesize that ZNF804A may affect grey matter volume (GMV) by interacting with COMT. Voxel-based morphometry was applied to analyze the main and interaction effects of ZNF804A rs1344706 and COMT rs4680 on brain GMV in 274 healthy young human subjects. The GMV of the left dorsolateral prefrontal cortex (DLPFC) showed a significant COMT rs4680 × ZNF804A rs1344706 interaction, manifesting as an inverted U-shape modulation by the presumed dopamine signaling. In COMT Met-allele carriers, the ZNF804A TG heterozygotes showed greater GMV in the left DLPFC than both GG and TT homozygotes. In COMT Val/Val homozygotes, however, the ZNF804A TG heterozygotes exhibited smaller GMV in the left DLPFC than GG homozygotes and comparable GMV with TT homozygotes. These findings suggest that ZNF804A affects the GMV of the prefrontal cortex by interacting with COMT, which may improve our understanding of neurobiological effect of ZNF804A and its association with schizophrenia.


ZNF804A COMT Single nucleotide polymorphism Grey matter volume Magnetic resonance imaging 


Compliance with ethical standards


This study was funded by the Natural Science Foundation of China (Grants number: 81425013, 81271551, 91132301, 81501451 and 81301201).

Conflict of interest

The authors declare no conflict of interest.

Ethical approval

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

Informed consent

Informed consent was obtained from all individual participants included in the study.

Supplementary material

11682_2016_9671_MOESM1_ESM.docx (104 kb)
ESM 1 (DOCX 104 kb)


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Copyright information

© Springer Science+Business Media New York 2017

Authors and Affiliations

  • Qiang Xu
    • 1
  • Yongqin Xiong
    • 1
  • Congcong Yuan
    • 1
  • Feng Liu
    • 1
  • Fangshi Zhao
    • 1
  • Junlin Shen
    • 1
  • Wen Qin
    • 1
  • Chunshui Yu
    • 1
  1. 1.Department of Radiology and Tianjin Key Laboratory of Functional ImagingTianjin Medical University General HospitalTianjinChina

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