Pan, Hong-xu, Wang, Yi-ge, Zhao, Yu-wen, Zeng, Qian, Wang, Zheng, Fang, Zheng-huan, Zhang, Yi, Zhou, Xun, He, Run-cheng, Xu, Qian, Sun, Qi-ying, Tan, Jie-qiong, Yan, Xin-xiang, Li, Jin-chen, Tang, Bei-sha, and Guo, Ji-feng
Recent studies have suggested ARSA , a gene responsible for metachromatic leukodystrophy, could be a genetic modifier of Parkinson's disease (PD) pathogenesis, acting as a molecular chaperone for α-synuclein. To elucidate the role of ARSA variants in PD, we did a comprehensive analysis of ARSA variants by performing next-generation sequencing on 477 PD families, 1440 sporadic early-onset PD patients and 1962 sporadic late-onset PD patients and 2636 controls from Chinese mainland, as well as the association between ARSA variants and cognitive function of PD patients. We identified 2 familial PD following autosomal dominant inherence carrying rare variants of ARSA , but they had limited clinical significance. We detected a total of 81 coding variants of ARSA in our subjects but none of the identified variants were associated with either susceptibility or cognitive performance of PD, while loss-of-function variants showed slightly increased burden in late-onset PD (0.25% vs. 0%, p = 0.08). Our results suggested ARSA may not play important roles in PD of Chinese population. [ABSTRACT FROM AUTHOR]