Genome-wide association study identifies common variants at four loci as genetic risk factors for Parkinson's disease
Genome-wide association study identifies common variants at four loci as genetic risk factors for Parkinson's disease
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DOI：
10.1038/ng.485
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发表时间：
2009-12-01
期刊：
影响因子：
30.8
通讯作者：
Toda, Tatsushi
中科院分区：
文献类型：
--
作者：
Satake, Wataru;Nakabayashi, Yuko;Toda, Tatsushi
为了确定帕金森病（PD）的易感性变异，我们在来自日本的2，011例病例和18，381例对照中进行了全基因组关联研究（GWAS）和两项重复研究。我们在1 q32上发现了一个新的易感基因座（P = 1.52 x 10（-12）），并将其命名为PARK 16，我们还在4p 15上发现了第二个新的风险基因座（P = 3.94 x 10（-9））。我们还检测到4 q22上的SNCA（P = 7.35 x 10（-17））和12 q12上的LRRK 2（P = 2.72 x 10（-8））的强相关性，这两个位点都与常染色体显性形式的帕金森综合征有关。通过比较对欧洲血统个体进行的GWAS的结果，我们确定PARK 16、SNCA和LRRK 2为PD的共享风险位点，BST 1和MAPT为显示群体差异的位点。我们的研究结果确定了两个新的PD易感基因座，常染色体显性帕金森病基因座参与典型的PD，并建议人口差异有助于遗传异质性PD。
To identify susceptibility variants for Parkinson's disease (PD), we performed a genome-wide association study (GWAS) and two replication studies in a total of 2,011 cases and 18,381 controls from Japan. We identified a new susceptibility locus on 1q32 (P = 1.52 x 10(-12)) and designated this as PARK16, and we also identified BST1 on 4p15 as a second new risk locus (P = 3.94 x 10(-9)). We also detected strong associations at SNCA on 4q22 (P = 7.35 x 10(-17)) and LRRK2 on 12q12 (P = 2.72 x 10(-8)), both of which are implicated in autosomal dominant forms of parkinsonism. By comparing results of a GWAS performed on individuals of European ancestry, we identified PARK16, SNCA and LRRK2 as shared risk loci for PD and BST1 and MAPT as loci showing population differences. Our results identify two new PD susceptibility loci, show involvement of autosomal dominant parkinsonism loci in typical PD and suggest that population differences contribute to genetic heterogeneity in PD.