Analysis of rare variants of autosomal‐dominant genes in a Chinese population with sporadic Parkinson’s disease

Molecular Genetics & Genomic Medicine

Jia‐Xian Dong¹  Jun Tian¹  Bao‐Rong Zhang¹  Ting Gao¹  Ran Zheng¹  Ya‐Ping Yan¹  Chong‐Yao Jin¹  Yang Ruan¹  Jia‐Li Pu¹  Ying Chen¹  Zhi‐Hao Lin¹ 

[1] Department of Neurology College of Medicine Second Affiliated HospitalZhejiang University Hangzhou Zhejiang China;

关键词: autosomal‐dominant genes;    gene‐based analysis;    Parkinson's disease;    rare variants;    sporadic;   

DOI  :  10.1002/mgg3.1449

来源: DOAJ

【 摘 要 】

Abstract Background To date, several studies have suggested that genes involved in monogenic forms of Parkinson's disease (PD) contribute to unrelated sporadic cases, but there is limited evidence in the Chinese population. Methods We performed a systematic analysis of 12 autosomal‐dominant PD (AD‐PD) genes (SNCA, LRRK2, GIGYF2, VPS35, EIF4G1, DNAJC13, CHCHD2, HTRA2, NR4A2, RIC3, TMEM230, and UCHL1) using panel sequencing and database filtration in a case‐control study of a cohort of 391 Chinese sporadic PD patients and unrelated controls. We evaluated the association between candidate variants and sporadic PD using gene‐based analysis. Results Overall, 18 rare variants were discovered in 18.8% (36/191) of the index patients. In addition to previously reported pathogenic mutations (LRRK2 p.Arg1441His and p.Ala419Val), another four unknown variants were found in LRRK2, which also contribute to PD risk (p = 0.002; odds ratio (OR) = 7.83, 95% confidence intervals (CI) = 1.76–34.93). The cumulative frequency of undetermined rare variants was significantly higher in PD patients (14.1%) than in controls (3.5%) (p = 0.0002; OR=4.54, 95% CI = 1.93‐10.69). Conclusion Our results confirm the strong impact of LRRK2 on the risk of sporadic PD, and also provide considerable evidence of the existence of additional undetermined rare variants in AD‐PD genes that contribute to the genetic etiology of sporadic PD in a Chinese cohort.

【 授权许可】

Unknown