Increased rate of sporadic and recurrent rare genic copy number variants in Parkinson's disease among Ashkenazi Jews
Increased rate of sporadic and recurrent rare genic copy number variants in Parkinson's disease among Ashkenazi Jews
复制标题
DOI：
10.1002/mgg3.18
复制
发表时间：
2013-09-01
影响因子：
2
通讯作者：
Clark, Lorraine N.
中科院分区：
文献类型：
--
作者：
Liu, Xinmin;Cheng, Rong;Clark, Lorraine N.
迄今为止，只有一个全基因组研究评估了拷贝数变异（CNV）对帕金森病（PD）的贡献。我们在德系犹太人（AJ）起源的病例对照数据集中（268例PD病例和178例对照）进行了全基因组CNV扫描。使用高置信度的CNVs，我们检查了全球基因组范围内的大（>= 100 kb）和罕见（= 29频率）的负担，发现病例比对照组高1.4倍（P = 0.019）。大的CNV（>= 500 kb）也与PD显著相关（P = 0.046，病例组比对照组高1.24倍）。对于罕见的CNV区域，全球负担升高。具体而言，对于Chr12p11.21上的OVOS2，仅在PD病例（n = 7）中观察到CNV，而在对照组中未观察到（P = 0.028），这一点得到了实验验证。共有81例PD病例携带对照组中不存在的罕见基因CNV。独创性途径分析（IPA）在与已知PD基因相同的疾病途径中识别出ATXN 3、FBXW 7、CHCHD 3、HSF 1、KLC 1和MBD 3。
To date, only one genome-wide study has assessed the contribution of copy number variants (CNVs) to Parkinson's disease (PD). We conducted a genome-wide scan for CNVs in a case-control dataset of Ashkenazi Jewish (AJ) origin (268 PD cases and 178 controls). Using high-confidence CNVs, we examined the global genome wide burden of large (>= 100 kb) and rare (= 29 frequency) were found 1.4 times more often in cases than in controls (P = 0.019). The large CNVs (>= 500 kb) were also significantly associated with PD ( P = 0.046, 1.24-fold higher in cases than in controls). Global burden was elevated for rare CNV regions. Specifically, for OVOS2 on Chr12p11.21, CNVs were observed only in PD cases (n = 7) but not in controls (P = 0.028) and this was experimentally validated. A total of 81 PD cases carried a rare genic CNV that was absent in controls. Ingenuity pathway analysis (IPA) identified ATXN3, FBXW7, CHCHD3, HSF1, KLC1, and MBD3 in the same disease pathway with known PD genes.