English (United Kingdom)

https://curated-unify.zendy.io/wp-json/zendy-region/v1/featured_content/oa?rat=en

https://curated-unify.zendy.io/wp-json/zendy-region/v1/highlighted_journal/

Global: Zendy Plus annual

Presents the access of premium content as premium feature

Premium Content

Presents the keyphrase highlighting as premium feature

Keyphrase Highlighting

Presents the summarisation as premium feature

Summarisation

Insights

Presents the pdf analysis as premium feature

PDF Analysis

Presents the zaia usage as premium feature

ZAIA

Global: Zendy Tools annual

Global: Zendy Free Plan

Global: Zendy Tools monthly

Global: Zendy Plus monthly

Schizophrenia (SCZ) is a severe psychiatric disorder with a strong genetic component. High heritability of SCZ suggests a major role for transmitted genetic variants. Furthermore, SCZ is also associated with a marked reduction in fecundity, leading to the hypothesis that alleles with large effects on risk might often occur de novo. In this study, we conducted whole-genome sequencing for 23 families from two cohorts with unaffected siblings and parents. Two nonsense de novo mutations (DNMs) in  GJC1  and  HIST1H2AD  were identified in SCZ patients. Ten genes ( DPYSL2, NBPF1, SDK1, ZNF595, ZNF718, GCNT2, SNX9, AACS, KCNQ1,  and  MSI2 ) were found to carry more DNMs in SCZ patients than their unaffected siblings by burden test. Expression analyses indicated that these DNM implicated genes showed significantly higher expression in prefrontal cortex in prenatal stage. The DNM in the  GJC1  gene is highly likely a loss function mutation (pLI = 0.94), leading to the dysregulation of ion channel in the glutamatergic excitatory neurons. Analysis of rare variants in independent exome sequencing dataset indicates that  GJC1  has significantly more rare variants in SCZ patients than in unaffected controls. Data from genome-wide association studies suggested that common variants in the  GJC1  gene may be associated with SCZ and SCZ-related traits. Genes co-expressed with  GJC1  are involved in SCZ, SCZ-associated pathways, and drug targets. These evidences suggest that  GJC1  may be a risk gene for SCZ and its function may be involved in prenatal and early neurodevelopment, a vulnerable period for developmental disorders such as SCZ.

translational psychiatry

Retracted: Identification of de novo mutations in prenatal neurodevelopment-associated genes in schizophrenia in two Han Chinese patient-sibling family-based cohorts