[基因名称]中的罕见变异与帕金森病的关联。（注：原文中“in ”后面缺少具体基因名称等相关内容，翻译是根据补充完整后的常规表述方式呈现，实际翻译需根据准确完整的原文信息来确定）

Association of rare variants in with Parkinson's disease.

作者信息

Senkevich Konstantin, Beletskaia Mariia, Dworkind Aliza, Yu Eric, Ahmad Jamil, Ruskey Jennifer A, Asayesh Farnaz, Spiegelman Dan, Fahn Stanley, Waters Cheryl, Monchi Oury, Dauvilliers Yves, Dupré Nicolas, Greenbaum Lior, Hassin-Baer Sharon, Nagornov Ilya, Tyurin Alexandr, Miliukhina Irina, Timofeeva Alla, Emelyanov Anton, Zakharova Ekaterina, Alcalay Roy N, Pchelina Sofya, Gan-Or Ziv

机构信息

The Neuro (Montreal Neurological Institute-Hospital), McGill University, Montreal, Quebec, Canada.

Department of Neurology and neurosurgery, McGill University, Montréal, QC, Canada, Canada.

出版信息

medRxiv. 2023 Mar 13:2023.03.08.23286773. doi: 10.1101/2023.03.08.23286773.

DOI:10.1101/2023.03.08.23286773

PMID:36993451

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10055435/

Abstract

BACKGROUND

Several lysosomal genes are associated with Parkinson's disease (PD), yet the association between PD and , which encodes for the enzyme arylsulfatase A, remains controversial.

OBJECTIVES

To evaluate the association between rare variants and PD.

METHODS

To study possible association of rare variants (minor allele frequency<0.01) in with PD, we performed burden analyses in six independent cohorts with a total of 5,801 PD patients and 20,475 controls, using optimized sequence Kernel association test (SKAT-O), followed by a meta-analysis.

RESULTS

We found evidence for an association between functional variants and PD in four independent cohorts (P≤0.05 in each) and in the meta-analysis (P=0.042). We also found an association between loss-of-function variants and PD in the UKBB cohort (P=0.005) and in the meta-analysis (P=0.049). However, despite replicating in four independent cohorts, these results should be interpreted with caution as no association survived correction for multiple comparisons. Additionally, we describe two families with potential co-segregation of the variant p.E384K and PD.

CONCLUSIONS

Rare functional and loss-of-function variants may be associated with PD. Further replication in large case-control cohorts and in familial studies is required to confirm these associations.

摘要

背景

多个溶酶体基因与帕金森病（PD）相关，但编码芳基硫酸酯酶A的基因与PD之间的关联仍存在争议。

目的

评估罕见基因变异与PD之间的关联。

方法

为研究基因中罕见变异（次要等位基因频率<0.01）与PD的可能关联，我们使用优化的序列核关联检验（SKAT-O），在六个独立队列（共5801例PD患者和20475例对照）中进行负担分析，随后进行荟萃分析。

结果

我们在四个独立队列（每个队列P≤0.05）和荟萃分析（P=0.042）中发现了功能基因变异与PD之间存在关联的证据。我们还在英国生物银行队列（P=0.005）和荟萃分析（P=0.049）中发现功能丧失变异与PD之间存在关联。然而，尽管在四个独立队列中得到了重复验证，但这些结果在经过多重比较校正后无关联，因此应谨慎解释。此外，我们描述了两个家系，其中基因变异p.E384K与PD可能存在共分离现象。