Mutational spectrum and clinical features of GBA1 variants in a Chinese cohort with Parkinson's disease.
Mutational spectrum and clinical features of GBA1 variants in a Chinese cohort with Parkinson's disease.
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DOI：
10.1038/s41531-023-00571-4
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发表时间：
2023-09-01
影响因子：
8.7
通讯作者：
Liu, Zhenhua
中科院分区：
文献类型：
--
作者：
Zhou, Yangjie;Wang, Yige;Wan, Juan;Zhao, Yuwen;Pan, Hongxu;Zeng, Qian;Zhou, Xun;He, Runcheng;Zhou, Xiaoxia;Xiang, Yaqin;Zhou, Zhou;Chen, Bin;Sun, Qiying;Xu, Qian;Tan, Jieqiong;Shen, Lu;Jiang, Hong;Yan, Xinxiang;Li, Jinchen;Guo, Jifeng;Tang, Beisha;Wu, Heng;Liu, Zhenhua
GBA1变异是帕金森病（PD）的重要危险因素。大多数评估gba1相关PD风险的研究都是在欧洲人群中进行的。虽然对中国人群GBA1基因的编码区进行了分析，但样本量不够。在这项研究中，我们旨在研究中国PD患者和健康对照者的GBA1变异，并探讨相关的临床特征。使用全外显子组和全基因组测序研究了4034例患者和2931例对照参与者的GBA1变异。采用多种量表对患者的临床特征进行评估。采用回归分析、卡方检验和Fisher精确检验分析GBA1变异和不同组的临床症状。我们鉴定出104个变体，其中包括8个新变体，扩大了GBA1变体的谱。PD患者GBA1变异频率为7.46%，高于对照组（1.81%）（P < 0.001，优势比[OR] = 4.38, 95%可信区间[CI]: 3.26-5.89）。重度变异体176例（4.36%），轻度变异体34例（0.84%），高危变异体3例（0.07%），未知变异体88例（2.18%）。我们的研究首次发现p.G241R （P = 0.007, OR = 15.3, 95% CI: 1.25-261.1）和p.S310G （P = 0.005, OR = 4.86, 95% CI: 1.52-28.04）变异增加了PD的风险。与没有GBA1变异的患者相比，GBA1变异的患者表现出更早的发病年龄和更高的可能的快速眼动睡眠行为障碍、嗅觉功能障碍、抑郁和自主神经功能障碍的风险。
GBA1 variants are important risk factors for Parkinson’s disease (PD). Most studies assessing GBA1-related PD risk have been performed in European-derived populations. Although the coding region of the GBA1 gene in the Chinese population has been analyzed, the sample sizes were not adequate. In this study, we aimed to investigate GBA1 variants in a large Chinese cohort of patients with PD and healthy control and explore the associated clinical characteristics. GBA1 variants in 4034 patients and 2931 control participants were investigated using whole-exome and whole-genome sequencing. The clinical features of patients were evaluated using several scales. Regression analysis, chi-square, and Fisher exact tests were used to analyze GBA1 variants and the clinical symptoms of different groups. We identified 104 variants, including 8 novel variants, expanding the spectrum of GBA1 variants. The frequency of GBA1 variants in patients with PD was 7.46%, higher than that in the control (1.81%) (P < 0.001, odds ratio [OR] = 4.38, 95% confidence interval [CI]: 3.26–5.89). Among patients, 176 (4.36%) had severe variants, 34 (0.84%) carried mild variants, three (0.07%) had risk variants, and 88 (2.18%) carried unknown variants. Our study, for the first time, found that p.G241R (P = 0.007, OR = 15.3, 95% CI: 1.25–261.1) and p.S310G (P = 0.005, OR = 4.86, 95% CI: 1.52–28.04) variants increased the risk of PD. Patients with GBA1 variants exhibited an earlier onset age and higher risk of probable rapid-eye-movement sleep behavior disorder, olfactory dysfunction, depression, and autonomic dysfunction than patients without GBA1 variants.
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影响因子：
9.2
作者：
Chang CC;Chow CC;Tellier LC;Vattikuti S;Purcell SM;Lee JJ
通讯作者：
Lee JJ
影响因子：
2.5
作者：
Jin, Hong;Chen, Jing;Liu, Chun-feng
通讯作者：
Liu, Chun-feng
影响因子：
12.6
作者：
Huang J;Cheng Y;Li C;Shang H
通讯作者：
Shang H
影响因子：
16.6
作者：
通讯作者：
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DOI：
10.1136/jnnp-2017-317348
发表时间：
2018-07
期刊：
Journal of neurology, neurosurgery, and psychiatry
影响因子：
--
作者：
Malek N;Weil RS;Bresner C;Lawton MA;Grosset KA;Tan M;Bajaj N;Barker RA;Burn DJ;Foltynie T;Hardy J;Wood NW;Ben-Shlomo Y;Williams NW;Grosset DG;Morris HR;PRoBaND clinical consortium
通讯作者：
PRoBaND clinical consortium