Genome wide study of tardive dyskinesia in schizophrenia

• Main Authors: Lim, Keane, Lam, Max, Zai, Clement, Tay, Jenny, Karlsson, Nina, Deshpande, Smita N., Thelma, B. K., Ozaki, Norio, Inada, Toshiya, Sim, Kang, Chong, Siow-Ann, Lencz, Todd, Liu, Jianjun, Lee, Jimmy
• Other Authors: Lee Kong Chian School of Medicine (LKCMedicine)
• Format: Article
• Language: English
• Published: 2022
• Subjects: Science::Medicine; Pharmacogenomics; Predictive Markers
• Online Access: https://hdl.handle.net/10356/154034
• Institution: Nanyang Technological University

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.