| Description |
GBA1 variants are important risk factors for Parkinson disease (PD). Most studies assessing GBA1-related PD risk have been performed in European-derived populations. There are some analysis of coding region of GBA1 gene in Asian population, while the sample sizes of which were not large. This study aims to investigate GBA1 variants in a large Chinese cohort of patients with PD and health controls, and explored their clinical characteristics. GBA1 variants in 4,034 patients and 2,931 controls were investigated using whole-exome sequencing (WES) and whole-genome sequencing (WGS). Clinical features of patients were evaluated using several scales. Regression analysis, chi-square, and Fisher exact tests were used to analyze the GBA1 variants and the clinical symptoms of different groups. In this study, 104 variants, including 42 novel variants, were identified, expanding the spectrum of GBA1 variants. The frequency of GBA1 variants in patients with PD was 7.46%, higher than that in the controls (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. Compared with patients without GBA1 variants, patients with GBA1 variants had an earlier age at onset, higher risk of probable rapid-eye-movement sleep behavior disorder, olfactory dysfunction, depression and autonomic dysfunction |
