Genome wide study of tardive dyskinesia in schizophrenia

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-Asi...

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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
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Online Access:https://hdl.handle.net/10356/154034
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spelling sg-ntu-dr.10356-1540342023-03-05T16:50:36Z Genome wide study of tardive dyskinesia in schizophrenia 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 Lee Kong Chian School of Medicine (LKCMedicine) Science::Medicine Pharmacogenomics Predictive Markers 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. Agency for Science, Technology and Research (A*STAR) Ministry of Health (MOH) National Medical Research Council (NMRC) Published version This research is supported by grants from the Ministry of Health Singapore, National Medical Research Council (Grant No.: NMRC/TCR/003/2008, NMRC/CG/ 004/2013). M.L. is supported by the National Medical Research Council Research Training Fellowship (Grant No.: MH095:003/008-1014). The work was (partly) supported by an A*STAR SPF grant to the SAPhIRE program. J.J.L. acknowledges the BMRC Central Research Fund (UIBR), Agency for Science, Technology and Research, Singapore and the BMRC Strategic Position Fund (SPF2014/001), Agency for Science, Technology and Research, Singapore. We thank the NIH for providing limited access datasets for the NIMH CATIE (ClinicalTrials.gov identifier NCT00014001, NIMH contract #N01MH90001). We would like to express our gratitude to Professor Arinami Tadao for his valuable comments. We also thank all participants and researchers who contributed to the collection of this data. 2022-02-08T06:45:43Z 2022-02-08T06:45:43Z 2021 Journal Article Lim, K., Lam, M., Zai, C., Tay, J., Karlsson, N., Deshpande, S. N., Thelma, B. K., Ozaki, N., Inada, T., Sim, K., Chong, S., Lencz, T., Liu, J. & Lee, J. (2021). Genome wide study of tardive dyskinesia in schizophrenia. Translational Psychiatry, 11(1), 351-. https://dx.doi.org/10.1038/s41398-021-01471-y 2158-3188 https://hdl.handle.net/10356/154034 10.1038/s41398-021-01471-y 34103471 2-s2.0-85107591955 1 11 351 en NMRC/CG/ 004/2013 MH095:003/008-1014 SPF2014/001 NMRC/TCR/003/2008 Translational Psychiatry © 2021 The Author(s). Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/. application/pdf
institution Nanyang Technological University
building NTU Library
continent Asia
country Singapore
Singapore
content_provider NTU Library
collection DR-NTU
language English
topic Science::Medicine
Pharmacogenomics
Predictive Markers
spellingShingle Science::Medicine
Pharmacogenomics
Predictive Markers
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
Genome wide study of tardive dyskinesia in schizophrenia
description 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.
author2 Lee Kong Chian School of Medicine (LKCMedicine)
author_facet Lee Kong Chian School of Medicine (LKCMedicine)
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
format Article
author 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
author_sort Lim, Keane
title Genome wide study of tardive dyskinesia in schizophrenia
title_short Genome wide study of tardive dyskinesia in schizophrenia
title_full Genome wide study of tardive dyskinesia in schizophrenia
title_fullStr Genome wide study of tardive dyskinesia in schizophrenia
title_full_unstemmed Genome wide study of tardive dyskinesia in schizophrenia
title_sort genome wide study of tardive dyskinesia in schizophrenia
publishDate 2022
url https://hdl.handle.net/10356/154034
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