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

Objective: Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is a hereditary cerebral small vessel disease caused by mutations in the gene. Previous studies have established a link between variants and Parkinson's disease (PD) in terms of neuropathology and clinical characteristics. In this study, we aimed to explore the role of 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 with PD. Although we did not find significant associations in the following genotype-phenotype analysis, the higher clinical scores of motor symptoms in -variant carriers were of interest.

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