The Association Between Lysosomal Storage Disorder Genes and Parkinson’s Disease: A Large Cohort Study in Chinese Mainland Population

Background: Recent years have witnessed an increasing number of studies indicating an essential role of the lysosomal dysfunction in Parkinson’s disease (PD) at the genetic, biochemical, and cellular pathway levels. In this study, we investigated the association between rare variants in lysosomal st...

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Autores principales: Yu-wen Zhao, Hong-xu Pan, Zhenhua Liu, Yige Wang, Qian Zeng, Zheng-huan Fang, Teng-fei Luo, Kun Xu, Zheng Wang, Xun Zhou, Runcheng He, Bin Li, Guihu Zhao, Qian Xu, Qi-ying Sun, Xin-xiang Yan, Jie-qiong Tan, Jin-chen Li, Ji-feng Guo, Bei-sha Tang
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Publicado: Frontiers Media S.A. 2021
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spelling oai:doaj.org-article:e91aa4c6c749496789aa5c4675283a092021-11-15T06:57:54ZThe Association Between Lysosomal Storage Disorder Genes and Parkinson’s Disease: A Large Cohort Study in Chinese Mainland Population1663-436510.3389/fnagi.2021.749109https://doaj.org/article/e91aa4c6c749496789aa5c4675283a092021-11-01T00:00:00Zhttps://www.frontiersin.org/articles/10.3389/fnagi.2021.749109/fullhttps://doaj.org/toc/1663-4365Background: Recent years have witnessed an increasing number of studies indicating an essential role of the lysosomal dysfunction in Parkinson’s disease (PD) at the genetic, biochemical, and cellular pathway levels. In this study, we investigated the association between rare variants in lysosomal storage disorder (LSD) genes and Chinese mainland PD.Methods: We explored the association between rare variants of 69 LSD genes and PD in 3,879 patients and 2,931 controls from Parkinson’s Disease & Movement Disorders Multicenter Database and Collaborative Network in China (PD-MDCNC) using next-generation sequencing, which were analyzed by using the optimized sequence kernel association test.Results: We identified the significant burden of rare putative LSD gene variants in Chinese mainland patients with PD. This association was robust in familial or sporadic early-onset patients after excluding the GBA variants but not in sporadic late-onset patients. The burden analysis of variant sets in genes of LSD subgroups revealed a suggestive significant association between variant sets in genes of sphingolipidosis deficiency disorders and familial or sporadic early-onset patients. In contrast, variant sets in genes of sphingolipidoses, mucopolysaccharidoses, and post-translational modification defect disorders were suggestively associated with sporadic late-onset patients. Then, SMPD1 and other four novel genes (i.e., GUSB, CLN6, PPT1, and SCARB2) were suggestively associated with sporadic early-onset or familial patients, whereas GALNS and NAGA were suggestively associated with late-onset patients.Conclusion: Our findings supported the association between LSD genes and PD and revealed several novel risk genes in Chinese mainland patients with PD, which confirmed the importance of lysosomal mechanisms in PD pathogenesis. Moreover, we identified the genetic heterogeneity in early-onset and late-onset of patients with PD, which may provide valuable suggestions for the treatment.Yu-wen ZhaoYu-wen ZhaoHong-xu PanHong-xu PanZhenhua LiuYige WangQian ZengZheng-huan FangTeng-fei LuoKun XuZheng WangXun ZhouRuncheng HeBin LiGuihu ZhaoQian XuQi-ying SunXin-xiang YanJie-qiong TanJin-chen LiJin-chen LiJin-chen LiJi-feng GuoJi-feng GuoJi-feng GuoJi-feng GuoBei-sha TangBei-sha TangBei-sha TangBei-sha TangFrontiers Media S.A.articleParkinson’s diseaselysosomal storage disorderslysosomeGBArare putative damaging variantsNeurosciences. Biological psychiatry. NeuropsychiatryRC321-571ENFrontiers in Aging Neuroscience, Vol 13 (2021)
institution DOAJ
collection DOAJ
language EN
topic Parkinson’s disease
lysosomal storage disorders
lysosome
GBA
rare putative damaging variants
Neurosciences. Biological psychiatry. Neuropsychiatry
RC321-571
spellingShingle Parkinson’s disease
lysosomal storage disorders
lysosome
GBA
rare putative damaging variants
Neurosciences. Biological psychiatry. Neuropsychiatry
RC321-571
Yu-wen Zhao
Yu-wen Zhao
Hong-xu Pan
Hong-xu Pan
Zhenhua Liu
Yige Wang
Qian Zeng
Zheng-huan Fang
Teng-fei Luo
Kun Xu
Zheng Wang
Xun Zhou
Runcheng He
Bin Li
Guihu Zhao
Qian Xu
Qi-ying Sun
Xin-xiang Yan
Jie-qiong Tan
Jin-chen Li
Jin-chen Li
Jin-chen Li
Ji-feng Guo
Ji-feng Guo
Ji-feng Guo
Ji-feng Guo
Bei-sha Tang
Bei-sha Tang
Bei-sha Tang
Bei-sha Tang
The Association Between Lysosomal Storage Disorder Genes and Parkinson’s Disease: A Large Cohort Study in Chinese Mainland Population
description Background: Recent years have witnessed an increasing number of studies indicating an essential role of the lysosomal dysfunction in Parkinson’s disease (PD) at the genetic, biochemical, and cellular pathway levels. In this study, we investigated the association between rare variants in lysosomal storage disorder (LSD) genes and Chinese mainland PD.Methods: We explored the association between rare variants of 69 LSD genes and PD in 3,879 patients and 2,931 controls from Parkinson’s Disease & Movement Disorders Multicenter Database and Collaborative Network in China (PD-MDCNC) using next-generation sequencing, which were analyzed by using the optimized sequence kernel association test.Results: We identified the significant burden of rare putative LSD gene variants in Chinese mainland patients with PD. This association was robust in familial or sporadic early-onset patients after excluding the GBA variants but not in sporadic late-onset patients. The burden analysis of variant sets in genes of LSD subgroups revealed a suggestive significant association between variant sets in genes of sphingolipidosis deficiency disorders and familial or sporadic early-onset patients. In contrast, variant sets in genes of sphingolipidoses, mucopolysaccharidoses, and post-translational modification defect disorders were suggestively associated with sporadic late-onset patients. Then, SMPD1 and other four novel genes (i.e., GUSB, CLN6, PPT1, and SCARB2) were suggestively associated with sporadic early-onset or familial patients, whereas GALNS and NAGA were suggestively associated with late-onset patients.Conclusion: Our findings supported the association between LSD genes and PD and revealed several novel risk genes in Chinese mainland patients with PD, which confirmed the importance of lysosomal mechanisms in PD pathogenesis. Moreover, we identified the genetic heterogeneity in early-onset and late-onset of patients with PD, which may provide valuable suggestions for the treatment.
format article
author Yu-wen Zhao
Yu-wen Zhao
Hong-xu Pan
Hong-xu Pan
Zhenhua Liu
Yige Wang
Qian Zeng
Zheng-huan Fang
Teng-fei Luo
Kun Xu
Zheng Wang
Xun Zhou
Runcheng He
Bin Li
Guihu Zhao
Qian Xu
Qi-ying Sun
Xin-xiang Yan
Jie-qiong Tan
Jin-chen Li
Jin-chen Li
Jin-chen Li
Ji-feng Guo
Ji-feng Guo
Ji-feng Guo
Ji-feng Guo
Bei-sha Tang
Bei-sha Tang
Bei-sha Tang
Bei-sha Tang
author_facet Yu-wen Zhao
Yu-wen Zhao
Hong-xu Pan
Hong-xu Pan
Zhenhua Liu
Yige Wang
Qian Zeng
Zheng-huan Fang
Teng-fei Luo
Kun Xu
Zheng Wang
Xun Zhou
Runcheng He
Bin Li
Guihu Zhao
Qian Xu
Qi-ying Sun
Xin-xiang Yan
Jie-qiong Tan
Jin-chen Li
Jin-chen Li
Jin-chen Li
Ji-feng Guo
Ji-feng Guo
Ji-feng Guo
Ji-feng Guo
Bei-sha Tang
Bei-sha Tang
Bei-sha Tang
Bei-sha Tang
author_sort Yu-wen Zhao
title The Association Between Lysosomal Storage Disorder Genes and Parkinson’s Disease: A Large Cohort Study in Chinese Mainland Population
title_short The Association Between Lysosomal Storage Disorder Genes and Parkinson’s Disease: A Large Cohort Study in Chinese Mainland Population
title_full The Association Between Lysosomal Storage Disorder Genes and Parkinson’s Disease: A Large Cohort Study in Chinese Mainland Population
title_fullStr The Association Between Lysosomal Storage Disorder Genes and Parkinson’s Disease: A Large Cohort Study in Chinese Mainland Population
title_full_unstemmed The Association Between Lysosomal Storage Disorder Genes and Parkinson’s Disease: A Large Cohort Study in Chinese Mainland Population
title_sort association between lysosomal storage disorder genes and parkinson’s disease: a large cohort study in chinese mainland population
publisher Frontiers Media S.A.
publishDate 2021
url https://doaj.org/article/e91aa4c6c749496789aa5c4675283a09
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