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

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Abstract

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.

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Authors and Affiliations

  1. Department of Radiology and Tianjin Key Laboratory of Functional Imaging, Tianjin Medical University General Hospital, No. 154, Anshan Road, Heping District, Tianjin, 300052, China

    Qiang Xu, Yongqin Xiong, Congcong Yuan, Feng Liu, Fangshi Zhao, Junlin Shen, Wen Qin & Chunshui Yu

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  1. Qiang Xu
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  2. Yongqin Xiong
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  3. Congcong Yuan
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  4. Feng Liu
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  5. Fangshi Zhao
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  6. Junlin Shen
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  7. Wen Qin
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  8. Chunshui Yu
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Correspondence to Chunshui Yu.

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Funding

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

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The authors declare no conflict of interest.

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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.

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

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Qiang Xu and Yongqin Xiong contributed equally to the work.

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Xu, Q., Xiong, Y., Yuan, C. et al. ZNF804A rs1344706 interacts with COMT rs4680 to affect prefrontal volume in healthy adults. Brain Imaging and Behavior 12, 13–19 (2018). https://doi.org/10.1007/s11682-016-9671-x

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