Association between variants of zinc finger genes and psychiatric disorders: systematic review and meta-analysis

Psychiatric disorders have a negative impact on society and human lives. Genetic factors are involved in the occurrence and development of psychiatric diseases. ZNF804A has been identified as one of the most compelling risk genes associated with broad phenotypes related to psychosis. We conducted a systematic meta-analysis and reviewed ZNF804A variants in psychosis-related disorders, including schizophrenia, bipolar disorder, and attention-deficit hyperactivity disorder. We also summarized the association between other zinc finger protein genes (ZNFs) and psychiatric diseases. The meta-analysis included a total of six variants of ZNF804A and three variants of other ZNFs (ZDHHC8 and ZKSCAN4), and the effects of ZNF variants on neurocognition and neuroimaging phenotypes were reviewed. The biological functions of these variants are also presented. We verified that ZNF804A was significantly related to psychiatric diseases, and the association between ZNF804A rs1344706 and psychosis (schizophrenia and bipolar disorder) did not vary with disease or ethnicity. The main brain area regulated by ZNF804A rs1344706 was the dorsolateral prefrontal cortex. The effect of ZNF804A variants on cognition did not display consistency with different diseases or methodologies. These findings suggest that ZNF804A might play an important role in common pathogenesis of psychiatric diseases, and its variants are likely involved in regulating the expression of psychosis-related genes, especially the dopamine pathway genes. Further research should focus on the molecular mechanisms by which ZNF804A variants act in psychiatric diseases and related phenotypes.