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Association Study of TAF1 Variants in Parkinson’s Disease

Increasing evidence reveals sex as an important factor in the development of Parkinson’s disease (PD), but associations between genes on the sex chromosomes and PD remain unknown. TAF1 is a gene located on the X chromosome which is known to cause X-linked syndromic mental retardation-33 (MRXS33) and...

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Autores principales: Zeng, Qian, Pan, Hongxu, Zhao, Yuwen, Wang, Yige, Xu, Qian, Tan, Jieqiong, Yan, Xinxiang, Li, Jinchen, Tang, Beisha, Guo, Jifeng
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9024305/
https://www.ncbi.nlm.nih.gov/pubmed/35464305
http://dx.doi.org/10.3389/fnins.2022.846095
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author Zeng, Qian
Pan, Hongxu
Zhao, Yuwen
Wang, Yige
Xu, Qian
Tan, Jieqiong
Yan, Xinxiang
Li, Jinchen
Tang, Beisha
Guo, Jifeng
author_facet Zeng, Qian
Pan, Hongxu
Zhao, Yuwen
Wang, Yige
Xu, Qian
Tan, Jieqiong
Yan, Xinxiang
Li, Jinchen
Tang, Beisha
Guo, Jifeng
author_sort Zeng, Qian
collection PubMed
description Increasing evidence reveals sex as an important factor in the development of Parkinson’s disease (PD), but associations between genes on the sex chromosomes and PD remain unknown. TAF1 is a gene located on the X chromosome which is known to cause X-linked syndromic mental retardation-33 (MRXS33) and X-linked Dystonia-Parkinsonism (XDP). In this study, we conducted whole-exome sequencing (WES) among 1,917 patients with early-onset or familial PD and 1,652 controls in a Chinese population. We detected a hemizygous frameshift variant c.29_53dupGGA(CAG)(2)CTACCATCA(CTG)(2)C (p.A19Dfs*50) in two unrelated male patients. Further segregation analysis showed an unaffected family member carried this variant, which suggested the penetrance of the variant may be age-related and incomplete. To verify the effects of TAF1 on PD, genetic analyses were carried separately by gender. Analysis of rare variants by optimal sequence kernel association (SKAT-O) test showed a nominally significant difference in variant burden between the male PD patients and controls (2.01 vs. 1.38%, p = 0.027). In the female group, none of the variant types showed significant association with PD in this study. In conclusion, we found rare variants in TAF1 may be implicated in PD, but further genetic and functional analyses were needed.
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spelling pubmed-90243052022-04-23 Association Study of TAF1 Variants in Parkinson’s Disease Zeng, Qian Pan, Hongxu Zhao, Yuwen Wang, Yige Xu, Qian Tan, Jieqiong Yan, Xinxiang Li, Jinchen Tang, Beisha Guo, Jifeng Front Neurosci Neuroscience Increasing evidence reveals sex as an important factor in the development of Parkinson’s disease (PD), but associations between genes on the sex chromosomes and PD remain unknown. TAF1 is a gene located on the X chromosome which is known to cause X-linked syndromic mental retardation-33 (MRXS33) and X-linked Dystonia-Parkinsonism (XDP). In this study, we conducted whole-exome sequencing (WES) among 1,917 patients with early-onset or familial PD and 1,652 controls in a Chinese population. We detected a hemizygous frameshift variant c.29_53dupGGA(CAG)(2)CTACCATCA(CTG)(2)C (p.A19Dfs*50) in two unrelated male patients. Further segregation analysis showed an unaffected family member carried this variant, which suggested the penetrance of the variant may be age-related and incomplete. To verify the effects of TAF1 on PD, genetic analyses were carried separately by gender. Analysis of rare variants by optimal sequence kernel association (SKAT-O) test showed a nominally significant difference in variant burden between the male PD patients and controls (2.01 vs. 1.38%, p = 0.027). In the female group, none of the variant types showed significant association with PD in this study. In conclusion, we found rare variants in TAF1 may be implicated in PD, but further genetic and functional analyses were needed. Frontiers Media S.A. 2022-04-08 /pmc/articles/PMC9024305/ /pubmed/35464305 http://dx.doi.org/10.3389/fnins.2022.846095 Text en Copyright © 2022 Zeng, Pan, Zhao, Wang, Xu, Tan, Yan, Li, Tang and Guo. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Neuroscience
Zeng, Qian
Pan, Hongxu
Zhao, Yuwen
Wang, Yige
Xu, Qian
Tan, Jieqiong
Yan, Xinxiang
Li, Jinchen
Tang, Beisha
Guo, Jifeng
Association Study of TAF1 Variants in Parkinson’s Disease
title Association Study of TAF1 Variants in Parkinson’s Disease
title_full Association Study of TAF1 Variants in Parkinson’s Disease
title_fullStr Association Study of TAF1 Variants in Parkinson’s Disease
title_full_unstemmed Association Study of TAF1 Variants in Parkinson’s Disease
title_short Association Study of TAF1 Variants in Parkinson’s Disease
title_sort association study of taf1 variants in parkinson’s disease
topic Neuroscience
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9024305/
https://www.ncbi.nlm.nih.gov/pubmed/35464305
http://dx.doi.org/10.3389/fnins.2022.846095
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