Abstract
Tardive dyskinesia (TD) is a severe condition characterized by repetitive involuntary movement of orofacial regions and extremities. Patients treated with antipsychotics typically present with TD symptomatology. Here, we conducted the largest GWAS of TD to date, by meta-analyzing samples of East-Asian, European, and African American ancestry, followed by analyses of biological pathways and polygenic risk with related phenotypes. We identified a novel locus and three suggestive loci, implicating immune-related pathways. Through integrating trans-ethnic fine mapping, we identified putative credible causal variants for three of the loci. Post-hoc analysis revealed that SNPs harbored in TNFRSF1B and CALCOCO1 independently conferred three-fold increase in TD risk, beyond clinical risk factors like Age of onset and Duration of illness to schizophrenia. Further work is necessary to replicate loci that are reported in the study and evaluate the polygenic architecture underlying TD.
Highlights
Introduction TardiveDyskinesia (TD) is a persistent and potentially debilitating involuntary movement disorder characterized by choreiform, athetoid, and or dystonic movements[1,2]
Commonly observed in patients with schizophrenia, Tardive dyskinesia (TD) can occur in individuals with other psychiatric disorders, as long as they have been exposed to prolonged antipsychotic treatment
The prevalence of TD in schizophrenia is estimated to be between 15 and 30%, rates of TD have reduced with prescription of second-generation antipsychotics[4–6]
Summary
Introduction TardiveDyskinesia (TD) is a persistent and potentially debilitating involuntary movement disorder characterized by choreiform, athetoid, and or dystonic movements[1,2]. Commonly observed in patients with schizophrenia, TD can occur in individuals with other psychiatric disorders, as long as they have been exposed to prolonged antipsychotic treatment. The prevalence of TD in schizophrenia is estimated to be between 15 and 30%, rates of TD have reduced with prescription of second-generation antipsychotics[4–6]. Second-generation antipsychotics still carry with them a risk of developing TD, and TD remains a clinically relevant phenotype as it has been associated with. As TD is potentially irreversible with no effective treatment, there needs to be an added emphasis on the prevention and identification of genetic risk factors. Genome-Wide Association Studies (GWAS) performed on the TD phenotype suggested that the GLI family zinc finger 2 (GLI2), heparan sulfate proteoglycan 2 (HSPG2), dipeptidyl-peptidase 6 (DPP6), and GABA pathway genes could putatively be considered
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