Alzheimer's disease and Parkinson's disease genome-wide association study top hits and risk of Parkinson's disease in Korean population

Abstract

Alzheimer's disease (AD) and Parkinson's disease (PD) have overlapping clinical and pathological features, suggesting a common pathway for these 2 neurodegenerative disorders. Here we investigated the association of both AD and PD GWAS top hits with PD susceptibility. We selected 25 single nucleotide polymorphisms (SNPs) in 9 genes (ABCA7, APOE, BST1, CLU, CR1, LRRK2, PARK16, PICALM, and SNCA) that were genotyped in 1036 PD case patients and 1208 controls. Case patients and controls were all ethnic Koreans. Logistic regression analysis was performed to calculate age- and sex-adjusted odds ratios. None of the AD-susceptibility loci (ABCA7, APOE, CLU, CR1, and PICALM) showed statistically significant association with PD susceptibility. In contrast, we replicated associations of SNCA, LRRK2, BST1, and PARK16 with PD susceptibility in Koreans. Of those, the SNCA SNP rs11931074 showed the most significant association with PD susceptibility (adjusted odds ratio = 1.48; 95% confidence interval = 1.31-1.67; p = 2.20E-10). In a logistic regression analysis with SNPs coded under an additive model, there was no significant genetic interaction between the LRRK2 and the PARK16 locus gene RAB7L1 in PD risk. Our results confirm the associations of SNCA, LRRK2, BST1, and PARK16 with PD susceptibility and fail to show significant associations of AD genome-wide association study (GWAS) top hits with PD susceptibility in a Korean population.

Keywords: Alzheimer's disease; Genetic association; Parkinson's disease; SNCA; Single nucleotide polymorphism.