Dataset Information

Association between NOTCH3 gene and Parkinson's disease based on whole-exome sequencing.

ABSTRACT:

Objective

Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is a hereditary cerebral small vessel disease caused by mutations in the NOTCH3 gene. Previous studies have established a link between NOTCH3 variants and Parkinson's disease (PD) in terms of neuropathology and clinical characteristics. In this study, we aimed to explore the role of NOTCH3 gene in PD in a large Chinese cohort.

Methods

A total of 1,917 patients with early-onset or familial PD and 1,652 matched controls were included. All variants were divided into common or rare types by minor allele frequency (MAF) at a threshold of 0.01 (MAF > 0.01 into common variants and others into rare variants). Common variants were subjected to single-variant tests by PLINK, then gene-based analyses were used for rare variants with the optimized sequence kernel association test (SKAT-O). For genotype-phenotype correlation assessment, regression models were conducted to compare clinical features between the studied groups.

Results

Three common variants (rs1044006, rs1043997, and rs1043994) showed a nominal protective effect against PD. However, none of these SNPs survived Bonferroni correction. The results in the validation cohort revealed a significant but opposite association between these variants and PD. The gene-based analyses of rare variants showed no significant associations of NOTCH3 with PD. Although we did not find significant associations in the following genotype-phenotype analysis, the higher clinical scores of motor symptoms in NOTCH3-variant carriers were of interest.

Conclusion

Our results indicated that NOTCH3 gene may not play an important role in the early-onset or familial PD of Chinese population.

SUBMITTER: Zeng Q

PROVIDER: S-EPMC9780269 | biostudies-literature | 2022

REPOSITORIES: biostudies-literature

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Publications

Association between <i>NOTCH3</i> gene and Parkinson's disease based on whole-exome sequencing.

Zeng Qian Q Pan Hongxu H Zhao Yuwen Y Wang Yige Y Xu Qian Q Tan Jieqiong J Yan Xinxiang X Li Jinchen J Tang Beisha B Guo Jifeng J

Frontiers in aging neuroscience 20221209

<h4>Objective</h4>Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is a hereditary cerebral small vessel disease caused by mutations in the <i>NOTCH3</i> gene. Previous studies have established a link between <i>NOTCH3</i> variants and Parkinson's disease (PD) in terms of neuropathology and clinical characteristics. In this study, we aimed to explore the role of <i>NOTCH3</i> gene in PD in a large Chinese cohort.<h4>Methods</h4>A total of 1,917 ...[more]

PMID: 36570541

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