Associations between the schizophrenia susceptibility gene ZNF804A and clinical outcomes in psychosis

Abstract

We sought to test the hypothesis that the rs1344706 A allele will be associated with worse clinical outcome in first-episode psychosis. A data linkage was set up between a large systematic study of first-episode psychosis and an electronic health-record case register at the South London and Maudsley NHS Foundation Trust—a large provider of secondary mental-health care. A sample of 291 patients, who presented with a first psychotic episode (ICD10 diagnoses F20–29 or F30–33) and in whom the rs1344706 genotype had been assayed, were followed to examine the duration of mental-health in-patient care during the 2 years following first service contact, as a primary outcome. Secondary outcome measures were whether or not an in-patient episode occurred and the number of in-patient episodes during this period. A strong association was found between the number of rs1344706 A alleles and the cumulative duration of mental-health in-patient stay over the 2 years since initial presentation. In the 84.2% who experienced an in-patient episode during this period, the mean duration of admission was an additional 38 days for each A allele increment. Therefore, in addition to its potential role as a risk factor for psychosis, the ZNF804A rs1344706 A allele is associated with worse clinical outcome.

Cohort profile of the South London and Maudsley NHS Foundation Trust Biomedical Research Centre (SLaM BRC) Case Register: current status and recent enhancement of an Electronic Mental Health Record-derived data resource

“… 52 Supplementing CRIS-derived outcomes to large clinical research samples with genetic profiling has also begun to generate novel output, for example, indicating that a well-recognised genetic risk factor for schizophrenia may also be a risk factor for worse clinical outcomes after diagnosis. 53 NLP applications have recently been extended to cover a range of affective and psychotic symptoms, allowing much more detailed phenotyping of large samples than a diagnosis alone provides, 54 55 and a range of adverse drug events have also recently been successfully captured. 56 …”

Epigenetic findings in periodontitis in UK twins: a cross sectional study

“…This CpG site is located within the 5’UTR of a protein coding gene, ZNF804A (Figure 1A). Polymorphisms of this gene confer increased susceptibility to mental health disorders such as schizophrenia and bipolar disorders, and contribute to heroin addiction [23]. CpG-site cg21245277 was significantly hypo-methylated in participants who experienced gingival bleeding (Figure 1B).…”

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

“…This SNP also showed an association with depressive symptoms improvement (HDRS), but only in the pooled bipolar sample. Literature data report several evidences supporting the role of rs1344706 in psychiatric disorders [12,[31][32][33][34][35][36]46,49], and with antidepressant response [25,40]. Regarding its association with psychosis, there were already some evidences indicating a possible correlation between this SNP and the psychotic phenotype [31], that indicated how rs1344706 may be able to mediate one of ZNF804A mRNA isoform, ZNF804AE3E4, during fetal life [31].…”

“…In this study, we investigated 7 single nucleotide polymorphisms (SNPs) within ZNF804A in two independent samples of Asian (Korean) and Caucasian (Italian) ancestry. We focused especially on rs1344706, an intronic SNPs solidly associated with psychiatric disorders [31][32][33][34][35][36], but we also evaluated other SNPs to increase the coverage of the gene.…”