Jiang Li, Pan Hong-Xu, Zhao Yu-Wen, Zeng Qian, Liu Zhen-Hua, Sun Qi-Ying, Xu Qian, Tan Jie-Qiong, Yan Xin-Xiang, Li Jin-Chen, Tang Bei-Sha, Guo Ji-Feng
Department of Neurology, Xiangya Hospital, Central South University, 410008, Changsha, Hunan, China; National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, 410008, Changsha, Hunan, China.
Department of Neurology, Xiangya Hospital, Central South University, 410008, Changsha, Hunan, China.
Parkinsonism Relat Disord. 2021 Mar;84:29-34. doi: 10.1016/j.parkreldis.2021.01.014. Epub 2021 Jan 28.
A recent study reported that rare variants in NUS1 were associated with Parkinson's disease (PD). We aimed to assess the relative contribution of rare and common coding/non-coding variants of NUS1 to late-onset PD patients (LOPD).
Whole genome sequencing data were analyzed for target NUS1 regions, derived from a cohort of 1962 cases and 1279 controls. The genetic association analyses were performed using logistic regression analysis and Sequence Kernel association test. Expression quantitative trait loci (eQTL) analysis was conducted to further explore the association of variants with NUS1 expression based on the data from GTEx database.
We identified 18 rare coding variants. p.Y131C was first identified in LOPD. However, no significant burden of rare NUS1 coding variants in LOPD was found. The rare variant sets of two regulatory elements (GH06J117605 and GH06J117674) were significantly enriched in LOPD even after Bonferroni correction (adjusted P = 0.013; adjusted P = 0.010). Considering the joint effect of rare and common variants, all variant sets within GH06J117605 and GH06J117674 showed association with LOPD but were no longer significant after Bonferroni correction. None of the common variants within coding/non-coding regions were significant after Bonferroni correction. The eQTL results suggested these variants in GH06J117605 and GH06J117674 could potentially have eQTL effects on the brain tissues.
These findings provide novel insight into the role of NUS1 regulatory regions in the development of LOPD and indicate that the variants in regulatory elements of NUS1 may be associated with LOPD by influencing the gene expression level.
最近一项研究报告称，NUS1基因中的罕见变异与帕金森病（PD）相关。我们旨在评估NUS1基因罕见和常见的编码/非编码变异对晚发性帕金森病患者（LOPD）的相对贡献。
对来自1962例病例和1279例对照队列的目标NUS1区域进行全基因组测序数据分析。使用逻辑回归分析和序列核关联检验进行遗传关联分析。基于GTEx数据库的数据进行表达定量性状位点（eQTL）分析，以进一步探索变异与NUS1表达的关联。
我们鉴定出18个罕见的编码变异。p.Y131C首次在LOPD中被鉴定出来。然而，在LOPD中未发现罕见的NUS1编码变异有显著负担。即使经过Bonferroni校正，两个调控元件（GH06J117605和GH06J117674）的罕见变异集在LOPD中仍显著富集（校正P = 0.013；校正P = 0.010）。考虑到罕见和常见变异的联合效应，GH06J117605和GH06J117674内的所有变异集均显示与LOPD相关，但经过Bonferroni校正后不再显著。编码/非编码区域内的常见变异在经过Bonferroni校正后均无显著性。eQTL结果表明，GH06J117605和GH06J117674中的这些变异可能对脑组织具有eQTL效应。
这些发现为NUS1调控区域在LOPD发生发展中的作用提供了新的见解，并表明NUS1调控元件中的变异可能通过影响基因表达水平与LOPD相关。
