Department of Neurology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea.
Neurobiol Aging. 2013 Nov;34(11):2695.e1-7. doi: 10.1016/j.neurobiolaging.2013.05.022. Epub 2013 Jun 29.
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.
阿尔茨海默病（AD）和帕金森病（PD）具有重叠的临床和病理特征，提示这两种神经退行性疾病存在共同的发病途径。在此，我们研究了 AD 和 PD 全基因组关联研究（GWAS）的 GWAS 研究结果与 PD 易感性的相关性。我们选择了 9 个基因（ABCA7、APOE、BST1、CLU、CR1、LRRK2、PARK16、PICALM 和 SNCA）中的 25 个单核苷酸多态性（SNP），并对 1036 名 PD 病例患者和 1208 名对照进行了基因分型。病例患者和对照均为韩国人。进行了逻辑回归分析以计算年龄和性别调整的优势比。AD 易感性基因座（ABCA7、APOE、CLU、CR1 和 PICALM）均未显示与 PD 易感性具有统计学意义的关联。相反，我们在韩国人群中复制了 SNCA、LRRK2、BST1 和 PARK16 与 PD 易感性的关联。在这些关联中，SNCA SNP rs11931074 与 PD 易感性的相关性最为显著（调整后的优势比=1.48；95%置信区间=1.31-1.67；p=2.20E-10）。在基于加性模型编码 SNP 的逻辑回归分析中，LRRK2 和 PARK16 基因 RAB7L1 之间在 PD 风险中没有明显的遗传相互作用。我们的结果证实了 SNCA、LRRK2、BST1 和 PARK16 与 PD 易感性的关联，并且在韩国人群中未能显示 AD 全基因组关联研究（GWAS）的 GWAS 研究结果与 PD 易感性的显著关联。
