title: ZNF804A rs1344706 interacts with COMT rs4680 to affect prefrontal volume in healthy adults.
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.
authors.affiliation: Department of Radiology and Tianjin Key Laboratory of Functional Imaging, Tianjin Medical University General Hospital, No. 154, Anshan Road, Heping District, Tianjin, 300052, China.
authors.forename: Qiang
authors.initials: Q
authors.lastname: Xu
authors.affiliation: Department of Radiology and Tianjin Key Laboratory of Functional Imaging, Tianjin Medical University General Hospital, No. 154, Anshan Road, Heping District, Tianjin, 300052, China.
authors.forename: Yongqin
authors.initials: Y
authors.lastname: Xiong
authors.affiliation: Department of Radiology and Tianjin Key Laboratory of Functional Imaging, Tianjin Medical University General Hospital, No. 154, Anshan Road, Heping District, Tianjin, 300052, China.
authors.forename: Congcong
authors.initials: C
authors.lastname: Yuan
authors.affiliation: Department of Radiology and Tianjin Key Laboratory of Functional Imaging, Tianjin Medical University General Hospital, No. 154, Anshan Road, Heping District, Tianjin, 300052, China.
authors.forename: Feng
authors.initials: F
authors.lastname: Liu
authors.affiliation: Department of Radiology and Tianjin Key Laboratory of Functional Imaging, Tianjin Medical University General Hospital, No. 154, Anshan Road, Heping District, Tianjin, 300052, China.
authors.forename: Fangshi
authors.initials: F
authors.lastname: Zhao
authors.affiliation: Department of Radiology and Tianjin Key Laboratory of Functional Imaging, Tianjin Medical University General Hospital, No. 154, Anshan Road, Heping District, Tianjin, 300052, China.
authors.forename: Junlin
authors.initials: J
authors.lastname: Shen
authors.affiliation: Department of Radiology and Tianjin Key Laboratory of Functional Imaging, Tianjin Medical University General Hospital, No. 154, Anshan Road, Heping District, Tianjin, 300052, China.
authors.forename: Wen
authors.initials: W
authors.lastname: Qin
authors.affiliation: Department of Radiology and Tianjin Key Laboratory of Functional Imaging, Tianjin Medical University General Hospital, No. 154, Anshan Road, Heping District, Tianjin, 300052, China. chunshuiyu@tijmu.edu.cn.
authors.forename: Chunshui
authors.initials: C
authors.lastname: Yu
mesh_terms: D000293:Adolescent; D000328:Adult; D002394:Catechol O-Methyltransferase / Q000235:genetics*; D004843:Epistasis, Genetic; D005260:Female; D007839:Functional Laterality; D060005:Genotyping Techniques; D066128:Gray Matter / Q000033:anatomy & histology / Q000000981:diagnostic imaging; D006579:Heterozygote; D006720:Homozygote; D006801:Humans; D007090:Image Interpretation, Computer-Assisted; D051741:Kruppel-Like Transcription Factors / Q000235:genetics*; D008279:Magnetic Resonance Imaging; D008297:Male; D009483:Neuropsychological Tests; D009929:Organ Size; D020641:Polymorphism, Single Nucleotide; D017397:Prefrontal Cortex / Q000033:anatomy & histology* / Q000000981:diagnostic imaging*; D055815:Young Adult
chemical_list: D051741:Kruppel-Like Transcription Factors; C540527:ZNF804A protein, human; C588010:COMT protein, human; D002394:Catechol O-Methyltransferase
keywords: COMT; Grey matter volume; Magnetic resonance imaging; Single nucleotide polymorphism; ZNF804A