In the present study we conducted a genome-wide association study (GWAS) in a cohort of 505 patients with paranoid schizophrenia (SCZ), of which 95 had tardive dyskinesia (TD), and 503 healthy controls. Using data generated by the PsychENCODE Consortium (PEC) and other bioinformatic databases, we revealed a gene network, implicated in neurodevelopment and brain function, associated with both these disorders. Almost all these genes are in gene or isoform co-expression PEC network modules important for the functioning of the brain; the activity of these networks is also altered in SCZ, bipolar disorder and autism spectrum disorders. The associated PEC network modules are enriched for gene ontology terms relevant to the brain development and function (CNS development, neuron development, axon ensheathment, synapse, synaptic vesicle cycle, and signaling receptor activity) and to the immune system (inflammatory response). Results of the present study suggest that orofacial and limbtruncal types of TD seem to share the molecular network with SCZ. Paranoid SCZ and abnormal involuntary movements that indicate the orofacial type of TD are associated with the same genomic loci on chromosomes 3p22.2, 8q21.13, and 13q14.2. The limbtruncal type of TD is associated with a locus on chromosome 3p13 where the best functional candidate is FOXP1, a high-confidence SCZ gene. The results of this study shed light on common pathogenic mechanisms for SCZ and TD, and indicate that the pathogenesis of the orofacial and limbtruncal types of TD might be driven by interacting genes implicated in neurodevelopment.

Original languageEnglish
Article number110134
Number of pages12
JournalProgress in Neuro-Psychopharmacology and Biological Psychiatry
Volume105
Early online date13 Oct 2020
DOIs
StatePublished - 1 Mar 2021

    Research areas

  • schizophrenia, tardive dyskinesia, GWAS, Gene networks, Regulatory sequence, Schizophrenia, Tardive dyskinesia, Genome-Wide Association Study, Humans, Schizophrenia, Paranoid/drug therapy, Tardive Dyskinesia/genetics, Forkhead Transcription Factors/genetics, Gene Regulatory Networks, Repressor Proteins/genetics, Antipsychotic Agents/adverse effects, Alleles, Polymorphism, Single Nucleotide, APP, RELIABILITY, CAUSE INTELLECTUAL DISABILITY, MOVEMENT-DISORDERS SADIMOD, RISK-FACTORS, TRANSCRIPTION, AMYLOID PRECURSOR PROTEIN, FOXP1, FUNCTION MUTATIONS CAUSE, INSIGHTS

    Scopus subject areas

  • Biological Psychiatry
  • Pharmacology

ID: 69855581