全基因组关联研究在荷兰人群中证实了现有的 PD 风险位点。
Genome-wide association study confirms extant PD risk loci among the Dutch.
机构信息
Department of Clinical Genetics, Section of Medical Genomics, VU University Medical Centre, Amsterdam, The Netherlands.
出版信息
Eur J Hum Genet. 2011 Jun;19(6):655-61. doi: 10.1038/ejhg.2010.254. Epub 2011 Jan 19.
In view of the population-specific heterogeneity in reported genetic risk factors for Parkinson's disease (PD), we conducted a genome-wide association study (GWAS) in a large sample of PD cases and controls from the Netherlands. After quality control (QC), a total of 514,799 SNPs genotyped in 772 PD cases and 2024 controls were included in our analyses. Direct replication of SNPs within SNCA and BST1 confirmed these two genes to be associated with PD in the Netherlands (SNCA, rs2736990: P = 1.63 × 10(-5), OR = 1.325 and BST1, rs12502586: P = 1.63 × 10(-3), OR = 1.337). Within SNCA, two independent signals in two different linkage disequilibrium (LD) blocks in the 3' and 5' ends of the gene were detected. Besides, post-hoc analysis confirmed GAK/DGKQ, HLA and MAPT as PD risk loci among the Dutch (GAK/DGKQ, rs2242235: P = 1.22 × 10(-4), OR = 1.51; HLA, rs4248166: P = 4.39 × 10(-5), OR = 1.36; and MAPT, rs3785880: P = 1.9 × 10(-3), OR = 1.19).
鉴于报道的帕金森病（PD）遗传风险因素在特定人群中的异质性，我们在荷兰的一个大样本 PD 病例和对照中进行了全基因组关联研究（GWAS）。经过质量控制（QC），我们对 772 例 PD 病例和 2024 例对照中 514799 个 SNP 进行了基因分型，这些 SNP 均包含在我们的分析中。SNCA 和 BST1 内 SNP 的直接复制证实了这两个基因与荷兰 PD 的相关性（SNCA，rs2736990：P = 1.63×10(-5)，OR = 1.325 和 BST1，rs12502586：P = 1.63×10(-3)，OR = 1.337）。在 SNCA 内，在基因的 3'和 5'末端的两个不同的连锁不平衡（LD）块中检测到两个独立的信号。此外，事后分析证实 GAK/DGKQ、HLA 和 MAPT 是荷兰 PD 的风险基因座（GAK/DGKQ，rs2242235：P = 1.22×10(-4)，OR = 1.51；HLA，rs4248166：P = 4.39×10(-5)，OR = 1.36；MAPT，rs3785880：P = 1.9×10(-3)，OR = 1.19）。
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