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Genome Wide Study of Tardive Dyskinesia in Schizophrenia

By Max Lam, Keane Lim, Jenny Tay, Nina Karlsson, Smita N Deshpande, BK Thelma, Norio Ozaki, Toshiya Inada, Kang Sim, Siow-Ann Chong, Jianjun Liu, Jimmy Lee

Posted 07 Aug 2018
bioRxiv DOI: 10.1101/386227

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. Multivariate analyses of polygenic risk for TD supports the genetic susceptibility of TD, with relatively lower allele frequencies variants being associated with TD, beyond that of antipsychotic medication. Together, these findings provide new insights into the genetic architecture and biology of TD.

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