Genetic analysis of dystonia-related genes in Parkinson's disease
-
Published:2023-05-26
Issue:
Volume:15
Page:
-
ISSN:1663-4365
-
Container-title:Frontiers in Aging Neuroscience
-
language:
-
Short-container-title:Front. Aging Neurosci.
Author:
Wang Yige,Zhao Yuwen,Pan Hongxu,Zeng Qian,Zhou Xiaoxia,Xiang Yaqin,Zhou Zhou,Xu Qian,Sun Qiying,Tan Jieqiong,Yan Xinxiang,Li Jinchen,Guo Jifeng,Tang Beisha,Yu Qiao,Liu Zhenhua
Abstract
ObjectiveParkinson's disease (PD) and dystonia are two closely related movement disorders with overlaps in clinical phenotype. Variants in several dystonia-related genes were demonstrated to be associated with PD; however, genetic evidence for the involvement of dystonia-related genes in PD has not been fully studied. Here, we comprehensively investigated the association between rare variants in dystonia-related genes and PD in a large Chinese cohort.MethodsWe comprehensively analyzed the rare variants of 47 known dystonia-related genes by mining the whole-exome sequencing (WES) and whole-genome sequencing (WGS) data from 3,959 PD patients and 2,931 healthy controls. We initially identified potentially pathogenic variants of dystonia-related genes in patients with PD based on different inheritance models. Sequence kernel association tests were conducted in the next step to detect the association between the burden of rare variants and the risk for PD.ResultsWe found that five patients with PD carried potentially pathogenic biallelic variants in recessive dystonia-related genes including COL6A3 and TH. Additionally, we identified 180 deleterious variants in dominant dystonia-related genes based on computational pathogenicity predictions and four of which were considered as potentially pathogenic variants (p.W591X and p.G820S in ANO3, p.R678H in ADCY5, and p.R458Q in SLC2A1). A gene-based burden analysis revealed the increased burden of variant subgroups of TH, SQSTM1, THAP1, and ADCY5 in sporadic early-onset PD, whereas COL6A3 was associated with sporadic late-onset PD. However, none of them reached statistical significance after the Bonferroni correction.ConclusionOur findings indicated that rare variants in several dystonia-related genes are suggestively associated with PD, and taken together, the role of COL6A3 and TH genes in PD is highlighted.
Funder
Natural Science Foundation of Hunan Province
National Natural Science Foundation of China
National Key Research and Development Program of China
Publisher
Frontiers Media SA
Subject
Cognitive Neuroscience,Aging
Cited by
1 articles.
订阅此论文施引文献
订阅此论文施引文献,注册后可以免费订阅5篇论文的施引文献,订阅后可以查看论文全部施引文献