Abstract
Background
The rs1344706 single nucleotide polymorphism in the ZNF804A gene has been associated with risk for psychosis in multiple genome-wide association
studies, yet mechanisms underlying this association are not known. Given preclinical
work suggesting an impact of ZNF804A on dopamine receptor gene transcription and clinical studies establishing dopaminergic
dysfunction in patients with schizophrenia, we hypothesized that the ZNF804A risk single nucleotide polymorphism would be associated with variation in dopamine
receptor availability in the human brain.
Methods
In this study, 72 healthy individuals genotyped for rs1344706 completed both [18F]fallypride and [11C]NNC-112 positron emission tomography scans to measure D2/D3 and D1 receptor availability, respectively. Genetic effects on estimates of binding potential
for each ligand were tested first with canonical subject-specific striatal regions
of interest analyses, followed by exploratory whole-brain voxelwise analyses to test
for more localized striatal signals and for extrastriatal effects.
Results
Region of interest analyses revealed significantly less D2/D3 receptor availability in risk-allele homozygotes (TT) compared with non-risk allele
carriers (G-allele carrier group: TG and GG) in the associative striatum and sensorimotor
striatum, but no significant differences in striatal D1 receptor availability.
Conclusions
These data suggest that ZNF804A genotype may be meaningfully linked to dopaminergic function in the human brain.
The results also may provide information to guide future studies of ZNF804A-related mechanisms of schizophrenia risk.
Keywords
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Article info
Publication history
Published online: December 21, 2020
Accepted:
December 15,
2020
Received in revised form:
December 3,
2020
Received:
October 13,
2020
Identification
Copyright
© 2020 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.
