Abstract
Functional and genetic studies have identified association between several Zinc finger (ZNF) proteins and Parkinson’s disease (PD). However, most of them were still awaiting further replications, especially in the Asian population. Here, we systematically selected PD-relevant ZNF genes and analyzed the genetic associations between these ZNFs and PD in a large Chinese PD cohort. We identified rare variants (minor allele frequency < 0.01) in 743 unrelated patients with early-onset PD (EOPD, age at onset < 50 years) using whole exome sequencing and evaluated the association between rare variants and EOPD at both allele and gene levels. Totally 91 rare variants were identified in ZNF746, ZNF646, ZNF184, ZNF165, ZND219, and GLIS1. One variant p.R373H in ZNF219 and two variants p.G161D and p.R158H in ZNF746 were significantly associated with EOPD, and gene-based burden analysis showed enrichment of rare variants of ZNF746 in EOPD. Our findings build up the connection between ZNF746 and PD from a genetic perspective for the first time, supplement current understanding for the genetic role of ZNFs in EOPD, and broaden the mutation spectrum in PD.
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All data generated or analyzed in the study were included in the article and supplementary material.
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Abbreviations
- PD:
-
Parkinson’s disease
- EOPD:
-
Early-onset Parkinson’s disease
- ZNF :
-
Zinc finger
- GWAS:
-
Genome-wide association study
- WES:
-
Whole exome sequencing
- MAF:
-
Minor allele frequency
- gnomAD:
-
Genome aggregation database
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Funding
This study was supported by the funding of the National Key Research and Development Program of China (Grant No. 2016YFC0901504); the 1.3.5 project for disciplines of excellence, West China Hospital, Sichuan University (No. ZYJC18038, No. ZYJC18003); the National Clinical Research Center for Geriatrics, West China Hospital, Sichuan University (Grant No. Z20192006); the Science Foundation of Chengdu Science and Technology Bureau (2019-YF05-00307-SN); and the Sichuan Science and Technology Program (Grant No. 2021YJ0415).
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ChunYu Li: design, execution, and writing. RuWei Ou: execution and writing. YongPing Chen: writing. XiaoJing Gu: blood samples collection. QianQian Wei: blood samples collection. Bei Cao: patients enrollment. LingYu Zhang: clinical data collection. YanBing Hou: patients enrollment. KunCheng Liu: clinical data collection. XuePing Chen: patients enrollment and clinical data collection. Wei Song: patients enrollment and clinical data collection. Bi Zhao: patients enrollment and clinical data collection. Ying Wu: patients enrollment and clinical data collection. Yi Liu: writing. HuiFang Shang: design, conception, and review.
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This study protocol was approved by the ethics committee of West China Hospital, Sichuan University. All participants have signed informed consent.
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Li, C.Y., Ou, R.W., Chen, Y.P. et al. Genetic Analysis of ZNF Protein Family Members for Early-Onset Parkinson’s Disease in Chinese Population. Mol Neurobiol 58, 3435–3442 (2021). https://doi.org/10.1007/s12035-021-02354-5
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DOI: https://doi.org/10.1007/s12035-021-02354-5