ZNF804A Gene Variants Have a Cross-diagnostic Influence on Psychosis and Treatment Improvement in Mood Disorders

Abstract

Objective: Genetic variations in the gene encoding zinc finger protein 804A gene (ZNF804A) have been associated with major depression and bipolar disorder. In this work we focused on the potential influence of ZNF804A variations on the risk of developing specific sub-phenotypes as well as the individual response to available treatments. Methods: We used two samples of different ethnic origin: a Korean sample, composed by 242 patients diagnosed with major depression and 132 patients diagnosed with bipolar disorder and 326 healthy controls; an Italian sample composed 151 major depression subjects, 189 bipolar disorder subjects and 38 outpatients diagnosed for a primary anxiety disorder. Results: Our analyses reported an association of rs1344706 with psychotic phenotype in the cross-diagnostic pooled sample (geno p = 4.15 × 10 −4 , allelic p = 1.06 × 10 −4). In the cross-diagnosis Italian sample but not in the Korean one, rs7597593 was involved with depressive symptoms improvement after treatment (geno p = 0.025, allelic p = 0.007). Conclusion: The present study evidenced the role of ZNF804A alterations in symptoms improvement after treatment. Both manic and depressive symptoms seem to be modulated by ZNF804A, though the latter was observed in the bipolar pooled sample only. The role of this factor is likely related to synaptic development and maintenance; however, further analyses will be needed to better understand the molecular mechanics involved with ZNF804A.

Subset-based method for cross-tissue transcriptome-wide association studies improves power and interpretability

“…Several of the novel genes identified have evidence in existing literature to be associated with BD and other neuropsychiatric processes ( Table 2 ). For example, ZNF280D , a protein-coding gene, is closely related to its family member ZNF804A , which has been identified as an important factor in bipolar disorder development 35 ; SULT1A3 , another protein-coding gene, has negative effects on sulfation and the impaired sulfation has been proved to have associations with many neurological diseases, such as bipolar disease 36 . Since such gene-based results primarily identify genetic loci, where multiple highly correlated genes can reside, we additionally clumped (See Supplementary for details) the associations based on genomic positions to identify the unique loci or genomic regions identified by each test.…”

Genetic neuroimaging of bipolar disorder: a systematic 2017–2020 update

“…ZNF804A rs1344706 is an intronic SNP which is associated with various psychiatric disorders, especially those characterised by psychosis, and affects depressive symptom improvement in BD after treatment (Calabrò et al, 2020). Zinc finger protein 804A is encoded in humans by the ZNF804A gene that maps to chromosome 2 q32.1; it consists of four exons coding for a 137 kDa protein, whose function is unknown, but its rs1344706 SNP was found to be related to diminished episodic and working memory in patients with schizophrenia (Walters et al, 2010) and to be associated with the self-rated paranoia/ self-reference schizotypal trait (Stefanis et al, 2013).…”

rs1344706 polymorphism of zinc finger protein 804a (ZNF804a) gene related to the integrity of white matter fiber bundle in schizophrenics

“…However, for the ZNF804a site rs1344706, it has been revealed that the GG homozygote of the ZNF804a site rs1344706 was related to the increased risk of early onset of SZ. It has also been suggested that the mutation of rs1344706 in ZNF804a gene may affect the cognitive function of SZ patients (32). There is also research revealing that ZNF804a site rs1344706 has no significant effects on the cognitive ability of SZ patients.…”