Department of Neurology, Singapore General Hospital, Singapore.
Neurology. 2010 Aug 10;75(6):508-12. doi: 10.1212/WNL.0b013e3181eccfcd.
A genome-wide association study (GWAS) in the Japanese population identified 2 new Parkinson disease (PD) susceptibility loci on 1q32 (PARK16) (OMIM 613164) and BST1. We analyzed single nucleotide polymorphism (SNPs) located at the GWAS-linked loci (PARK16, PARK8, PARK1, and BST1) in a Chinese population and also conducted a meta-analysis in Asians by pooling 2 independent replication studies from Japan.
We conducted an analysis of 13 SNPs associated with PD GWAS-linked loci in 2 case-control cohorts comprised of 1,349 ethnic Chinese subjects.
PARK16, PARK8, and PARK1 loci but not BST1 were found to be associated with PD. PARK16 SNPs were associated with a decreased risk while PARK1 and PARK8 SNPs were associated with an increased risk of PD. A pooled analysis of our Chinese cohorts and 2 Japanese replication cohorts involving 1,366 subjects with PD and 16,669 controls revealed robust association with these 3 loci and also BST1. There was a trend toward a stronger protective effect of SNPs at the PARK16 locus in sporadic PD compared to familial cases and in older compared to younger subjects.
Our study reaffirms the role of GWAS-linked loci in PD in Asian subjects and the strength of association is similar between Chinese and Japanese subjects. Efforts to elucidate the associated gene within PARK16 locus are warranted.
一项在日本人群中进行的全基因组关联研究（GWAS）发现了两个新的帕金森病（PD）易感位点，位于 1q32（PARK16）（OMIM 613164）和 BST1。我们分析了中国人群中与 GWAS 相关的单核苷酸多态性（SNP）位点（PARK16、PARK8、PARK1 和 BST1），并通过合并来自日本的 2 项独立的复制研究，对亚洲人群进行了荟萃分析。
我们对包含 1349 名汉族个体的 2 个病例对照队列中与 PD GWAS 相关的 13 个 SNP 进行了分析。
发现 PARK16、PARK8 和 PARK1 位点而非 BST1 与 PD 相关。PARK16 SNP 与 PD 风险降低相关，而 PARK1 和 PARK8 SNP 与 PD 风险增加相关。我们的中国队列和 2 个日本复制队列的荟萃分析，共纳入了 1366 名 PD 患者和 16669 名对照者，揭示了这些 3 个位点和 BST1 与 PD 之间存在显著关联。与家族性病例相比，散发性 PD 中 PARK16 位点 SNP 的保护作用更强，与老年个体相比，年轻个体的保护作用更强，这种趋势具有统计学意义。
本研究再次证实了 GWAS 相关的 PD 易感位点在亚洲人群中的作用，并且中国和日本人群之间的关联强度相似。有必要努力阐明 PARK16 位点相关的基因。
