Research Division, Institute of Mental Health, Singapore, Singapore.
Zucker Hillside Hospital, New York, NY, USA.
Transl Psychiatry. 2021 Jun 8;11(1):351. doi: 10.1038/s41398-021-01471-y.
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.
迟发性运动障碍（TD）是一种严重的病症，其特征是口腔和面部区域及四肢出现重复性无意识运动。接受抗精神病药物治疗的患者通常会出现 TD 症状。在这里，我们通过对东亚、欧洲和非裔美国人样本进行荟萃分析，进行了迄今为止最大的 TD GWAS 研究，随后对生物途径和与相关表型的多基因风险进行了分析。我们确定了一个新的基因座和三个提示性基因座，提示与免疫相关的途径。通过整合跨种族精细映射，我们确定了三个基因座的潜在可信因果变异。事后分析显示，TNFRSF1B 和 CALCOCO1 中所含的 SNPs 独立地使 TD 风险增加了三倍，超出了发病年龄和精神分裂症发病持续时间等临床危险因素。有必要进一步开展工作来复制该研究中报告的基因座，并评估 TD 背后的多基因结构。
