Evidence map›Paper›PMID 41904258›Full record

ArticleNPJ Parkinson's disease2026

The genetic spectrum of LRRK2 variants in Parkinson's disease: findings from a large Chinese cohort.

Juan Wan, Hongxu Pan, Dong Chang, Yuwen Zhao, Qian Xu, Lingyan Yao, Qiying Sun, Xuewei Zhang, Runcheng He, Chunyu Wang and 47 more

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Article in NPJ Parkinson's disease, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

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1citing papers in PubMed
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1 · What the graph read from it

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3 · Its place in the literature

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1 citing paper in PubMed.

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4 · The record

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5 · Who and what money

Authors and funding

57 authors.

Juan Wan *Department of Neurology, Multi-Omics Research Center for Brain Disorders, The First Affiliated Hospital, Hengyang Medical School, University of South China, Hengyang, China.
Hongxu Pan *Department of Neurology, Xiangya Hospital, Central South University, Changsha, China.
Dong Chang *Department of Neurology, Multi-Omics Research Center for Brain Disorders, The First Affiliated Hospital, Hengyang Medical School, University of South China, Hengyang, China.
Yuwen ZhaoDepartment of Neurology, Xiangya Hospital, Central South University, Changsha, China.
Qian XuDepartment of Neurology, Xiangya Hospital, Central South University, Changsha, China.
Lingyan YaoNational Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, China.
Qiying SunNational Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, China.
Xuewei ZhangDepartment of Health Management Center, Xiangya Hospital, Central South University, Changsha, China.
Runcheng HeDepartment of Neurology, The Second Xiangya Hospital, Central South University, Changsha, China.
Chunyu WangDepartment of Neurology, The Second Xiangya Hospital, Central South University, Changsha, China.
Hainan ZhangDepartment of Neurology, The Second Xiangya Hospital, Central South University, Changsha, China.
Lifang LeiDepartment of Neurology, The Third Xiangya Hospital, Central South University, Changsha, China.
Yuzheng WangDepartment of Neurology, Multi-Omics Research Center for Brain Disorders, The First Affiliated Hospital, Hengyang Medical School, University of South China, Hengyang, China.
Mingqiang LiDepartment of Neurology, Multi-Omics Research Center for Brain Disorders, The First Affiliated Hospital, Hengyang Medical School, University of South China, Hengyang, China.
Heng WuDepartment of Neurology, Multi-Omics Research Center for Brain Disorders, The First Affiliated Hospital, Hengyang Medical School, University of South China, Hengyang, China.
Jinghong MaDepartment of Neurology, National Clinical Research Center for Geriatric Diseases, Xuanwu Hospital of Capital Medical University, Beijing, China.
Yiwen WuDepartment of Neurology, Ruijin Hospital, affiliated with Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Yan XuDepartment of Neurology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
Nian XiongDepartment of Neurology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
Tao WangDepartment of Neurology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
Xuejing WangDepartment of Neurology, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong, China.
Ling ChenDepartment of Neurology, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong, China.
Yanming XuDepartment of Neurology, West China Hospital, Sichuan University, Chengdu, China.
Hongmei CaoDepartment of Neurology, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China.
Kezhong ZhangDepartment of Neurology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China.
Weiguo LiuDepartment of Neurology, Affiliated Brain Hospital of Nanjing Medical University, Nanjing, China.
Yuhu ZhangDepartment of Neurology, Guangdong Provincial People's Hospital, Guangzhou, Guangdong, China.
Chengjie MaoDepartment of Neurology, The Second Affiliated Hospital of Soochow University, Suzhou, China.
Qing WangDepartment of Neurology, Zhujiang Hospital of Southern Medical University, Guangzhou, Guangdong, China.
Zheng XueDepartment of Neurology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
Zhentao ZhangDepartment of Neurology, Renmin Hospital of Wuhan University, Wuhan, China.
Oumei ChengDepartment of Neurology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China.
Wei HuangDepartment of Neurology, The Second Affiliated Hospital of Nanchang University, Nanchang, China.
Guohua ZhaoDepartment of Neurology, The Fourth Affiliated Hospital, International Institutes of Medicine, Zhejiang University, Jinhua, China.
Guiyun CuiDepartment of Neurology, The Affiliated Hospital of Xuzhou Medical University, Xuzhou, China.
Tao ChenDepartment of Neurology, Hainan General Hospital, Hainan Affiliated Hospital of Hainan Medical University, Haikou, China.
Puqing WangDepartment of Neurology, Xiang Yang No. 1 People's Hospital Affiliated to Hubei University of Medicine, Xiangyang, China.
Wei DiDepartment of Neurology, Shaanxi Provincial People's Hospital, Xi'an, China.
Hong LiuDepartment of Neurology, Heping Hospital Affiliated to Changzhi Medical College, Changzhi, China.
Houfeng ZhengSuzhou Laboratory of Precision Health and Data Science, The Second Affiliated Hospital of Soochow University, Suzhou, China.
Chao ChenCentre for Medical Genetics & Hunan Key Laboratory of Medical Genetics, School of Life Sciences, Central South University, Changsha, China.
Hui GuoCentre for Medical Genetics & Hunan Key Laboratory of Medical Genetics, School of Life Sciences, Central South University, Changsha, China.
Kun XiaCentre for Medical Genetics & Hunan Key Laboratory of Medical Genetics, School of Life Sciences, Central South University, Changsha, China.
Zhuohua ZhangCentre for Medical Genetics & Hunan Key Laboratory of Medical Genetics, School of Life Sciences, Central South University, Changsha, China.
Kai YuanNational Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, China.
Jinchen LiNational Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, China.
Junling WangDepartment of Neurology, Xiangya Hospital, Central South University, Changsha, China.
Jifeng GuoDepartment of Neurology, Xiangya Hospital, Central South University, Changsha, China.
Lu ShenDepartment of Neurology, Xiangya Hospital, Central South University, Changsha, China.
Hong JiangDepartment of Neurology, Xiangya Hospital, Central South University, Changsha, China.
Chunfeng LiuDepartment of Neurology, The Second Affiliated Hospital of Soochow University, Suzhou, China.
Jun LiuDepartment of Neurology, Ruijin Hospital, affiliated with Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Piu ChanDepartment of Neurology, National Clinical Research Center for Geriatric Diseases, Xuanwu Hospital of Capital Medical University, Beijing, China.
Zhenhua LiuDepartment of Neurology, Xiangya Hospital, Central South University, Changsha, China. liuzhenhua@csu.edu.cn.
Beisha TangDepartment of Neurology, Multi-Omics Research Center for Brain Disorders, The First Affiliated Hospital, Hengyang Medical School, University of South China, Hengyang, China. bstang7398@163.com.
Parkinson’s Disease & Movement Disorders Multicenter Database and Collaborative Network in China (PD-MDCNC)
China Essential Tremor Alliance (CETA)

Funding

the China Postdoctoral Science Foundation - Hunan Joint Support Program 2025T025HNthe Clinical Medical Research "4310" Program of the University of South China 20214310NHYCG08the National Key Research and Development Program of China 2021YFC2501204the National Natural Science Foundation of China 82501518the Postdoctoral Fellowship Program of CPSF GZC20251437the Science and Technology Major Project of Hunan Provincial Science and Technology Department 2021SK1010
6 · The paper itself

Abstract

The pathogenicity of variants of uncertain significance in the LRRK2 gene remains underexplored. Investigating the LRRK2 variant spectrum in a large Chinese population cohort can provide deeper insights into its pathogenic mechanisms. This study examined the LRRK2 gene variants in 20,519 Chinese individuals, including 7,562 Parkinson's disease (PD) patients, 3,077 Essential tremor (ET) patients, and 9880 healthy controls. We conducted a genetic analysis of low-frequency and common non-synonymous variants in the LRRK2 gene across the cohorts. A total of 287 low-frequency non-synonymous LRRK2 variants were identified in the PD and control cohorts. Among these, six reported pathogenic variants (p.R1325Q, p.R1441C, p.R1441H, p.V1447M, p.G2019S, p.I2020T) and three reported likely pathogenic variants (p.R1067Q, p.N1437D, p.R1728H) were enriched in PD cases, with a frequency of 0.71%. In contrast, only one pathogenic variant (p.R1325Q) and one likely pathogenic variant (p.R1067Q) were observed in healthy controls (0.11%), and the ET cohort exhibited similar variant distribution to controls (0.19%). Burden analysis and association analysis revealed novel likely pathogenic variants, including p.A312V, p.M968K, and p.R1320S as candidates. These novel variants were significantly more frequent in PD patients (0.79%) compared to healthy controls (0.20%) or ET patients (0.42%). Additionally, seven common missense variants of LRRK2 were identified, and significant associations with PD for p.A419V, p.R1628P, and p.G2385R were confirmed, but no common variants were linked to ET. This study provides the first comprehensive characterization of the LRRK2 variant spectrum in a large Chinese population, underscoring the pivotal role of LRRK2 in PD pathogenesis but not in ET. These findings advance the understanding of LRRK2 in neurodegenerative disorders and lay a foundation for personalized therapeutic strategies based on genetic profiling.

Identifiers

PMID41904258
PMCPMC13194747

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