The role of genetics in Parkinson's disease: A large cohort study in Chinese mainland population

Yuwen Zhao, Lixia Qin, Hongxu Pan, Zhenhua Liu, Li Jiang, Yan He, Qian Zeng, Xun Zhou, Xiaoxia Zhou, Yangjie Zhou, Zhenghuan Fang, Zheng Wang, Yaqin Xiang, Honglan Yang, Yige Wang, Kailin Zhang, Rui Zhang, Runcheng He, Xiaoting Zhou, Zhou ZhouNannan Yang, Dongxiao Liang, Juan Chen, Xuxiang Zhang, Yao Zhou, Hongli Liu, Penghui Deng, Kun Xu, Ke Xu, Chaojun Zhou, Junfei Zhong, Qian Xu, Qiying Sun, Bin Li, Guihu Zhao, Tao Wang, Ling Chen, Huifang Shang, Weiguo Liu, Piu Chan, Zheng Xue, Qing Wang, Li Guo, Xuejing Wang, Changshui Xu, Zhentao Zhang, Tao Chen, Lifang Lei, Hainan Zhang, Chunyu Wang, Jieqiong Tan, Xinxiang Yan, Lu Shen, Hong Jiang, Zhuohua Zhang, Zhengmao Hu, Kun Xia, Zhenyu Yue, Jinchen Li, Jifeng Guo, Beisha Tang

Research output: Contribution to journalArticlepeer-review

88 Scopus citations


This study aimed to determine the mutational spectrum of familial Parkinson's disease and sporadic early-onset Parkinson's disease (sEOPD) in a mainland Chinese population and the clinical features of mutation carriers. We performed multiplex ligation-dependent probe amplification assays and whole-exome sequencing for 1676 unrelated patients with Parkinson's disease in a mainland Chinese population, including 192 probands from families with autosomal-recessive Parkinson's disease, 242 probands from families with autosomal-dominant Parkinson's disease, and 1242 sEOPD patients (age at onset 4 50). According to standards and guidelines from the American College of Medical Genetics and Genomics, pathogenic/likely pathogenic variants in 23 known Parkinson's disease-associated genes occurred more frequently in the autosomal-recessive Parkinson's disease cohort (65 of 192, 33.85%) than in the autosomal-dominant Parkinson's disease cohort (10 of 242, 4.13%) and the sEOPD cohort (57 of 1242, 4.59%), which leads to an overall molecular diagnostic yield of 7.88% (132 of 1676). We found that PRKN was the most frequently mutated gene (n = 83, 4.95%) and present the first evidence of an SNCA duplication and LRRK2 p.N1437D variant in mainland China. In addition, several novel pathogenic/likely pathogenic variants including LRRK2 (p.V1447M and p.Y1645S), ATP13A2 (p.R735X and p.A819D), FBXO7 (p.G67E), LRP10 (c.322dupC/p.G109Rfs*51) and TMEM230 (c.429delT/ p.P144Qfs*2) were identified in our cohort. Furthermore, the age at onset of the 132 probands with genetic diagnoses (median, 31.5 years) was about 14.5 years earlier than that of patients without molecular diagnoses (i.e. non-carriers, median 46.0 years). Specifically, the age at onset of Parkinson's disease patients with pathogenic/likely pathogenic variants in ATP13A2, PLA2G6, PRKN, or PINK1 was significantly lower than that of non-carriers, while the age at onset of carriers with other gene pathogenic/ likely pathogenic variants was similar to that of non-carriers. The clinical spectrum of Parkinson's disease-associated gene carriers in this mainland Chinese population was similar to that of other populations. We also detected 61 probands with GBA possibly pathogenic variants (3.64%) and 59 probands with GBA p.L444P (3.52%). These results shed insight into the genetic spectrum and clinical manifestations of Parkinson's disease in mainland China and expand the existing repertoire of pathogenic or likely pathogenic variants involved in known Parkinson's disease-associated genes. Our data highlight the importance of genetic testing in Parkinson's disease patients with age at onset 5 40 years, especially in those from families with a recessive inheritance pattern, who may benefit from early diagnosis and treatment.

Original languageEnglish
Pages (from-to)2220-2234
Number of pages15
Issue number7
StatePublished - 1 Jul 2020


  • Age at onset
  • Disease-associated gene
  • Parkinson's disease
  • Pathogenic or likely pathogenic variant
  • Whole-exome sequencing


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