Dissection of the genetics of Parkinson's disease identifies an additional association 5' of SNCA and multiple associated haplotypes at 17q21.
Dissection of the genetics of Parkinson's disease identifies an additional association 5' of SNCA and multiple associated haplotypes at 17q21.
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DOI：
10.1093/hmg/ddq469
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发表时间：
2011-01-15
影响因子：
3.5
通讯作者：
Wood NW
中科院分区：
文献类型：
--
作者：
UK Parkinson's Disease Consortium;Wellcome Trust Case Control Consortium 2;Spencer CC;Plagnol V;Strange A;Gardner M;Paisan-Ruiz C;Band G;Barker RA;Bellenguez C;Bhatia K;Blackburn H;Blackwell JM;Bramon E;Brown MA;Brown MA;Burn D;Casas JP;Chinnery PF;Clarke CE;Corvin A;Craddock N;Deloukas P;Edkins S;Evans J;Freeman C;Gray E;Hardy J;Hudson G;Hunt S;Jankowski J;Langford C;Lees AJ;Markus HS;Mathew CG;McCarthy MI;Morrison KE;Palmer CN;Pearson JP;Peltonen L;Pirinen M;Plomin R;Potter S;Rautanen A;Sawcer SJ;Su Z;Trembath RC;Viswanathan AC;Williams NW;Morris HR;Donnelly P;Wood NW
我们在1705名帕金森病（PD）英国患者和5175名英国对照中进行了全基因组关联研究（GWAS），这是迄今为止PD GWAS的最大样本量。在27个地区的1039例法国PD病例和1984例对照的额外队列中进行了复制，显示出最强的相关性证据（P< 10−4）。我们复制了已发表的4 q22/SNCA和17 q21/MAPT染色体区域的相关性（P< 10−10），并发现了4 q22/SNCA中存在额外独立相关性的证据。对17 q21单倍型结构的详细分析表明，该区域内存在三个独立的风险组。我们发现了位于三个先前发表的相关区域（4p 15/BST 1，4p 16/GAK和1 q32/PARK 16）的常见变异的关联性弱但一致的证据。我们发现没有支持先前报道的SNP关联在12 q12/LRRK 2。我们还发现4 q22/SNCA中的两个SNPs与疾病发病年龄相关。
We performed a genome-wide association study (GWAS) in 1705 Parkinson's disease (PD) UK patients and 5175 UK controls, the largest sample size so far for a PD GWAS. Replication was attempted in an additional cohort of 1039 French PD cases and 1984 controls for the 27 regions showing the strongest evidence of association (P< 10−4). We replicated published associations in the 4q22/SNCA and 17q21/MAPT chromosome regions (P< 10−10) and found evidence for an additional independent association in 4q22/SNCA. A detailed analysis of the haplotype structure at 17q21 showed that there are three separate risk groups within this region. We found weak but consistent evidence of association for common variants located in three previously published associated regions (4p15/BST1, 4p16/GAK and 1q32/PARK16). We found no support for the previously reported SNP association in 12q12/LRRK2. We also found an association of the two SNPs in 4q22/SNCA with the age of onset of the disease.
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DOI：
10.1038/nrg2579
发表时间：
2009-06
期刊：
Nature reviews. Genetics
影响因子：
--
作者：
Cordell HJ
通讯作者：
Cordell HJ
影响因子：
30.8
作者：
Marchini, Jonathan;Howie, Bryan;Donnelly, Peter
通讯作者：
Donnelly, Peter
影响因子：
2.5
作者：
Evans, W;Fung, HC;Hardy, J
通讯作者：
Hardy, J
影响因子：
11
作者：
HUGHES, AJ;DANIEL, SE;LEES, AJ
通讯作者：
LEES, AJ
影响因子：
30.8
作者：
Satake, Wataru;Nakabayashi, Yuko;Toda, Tatsushi
通讯作者：
Toda, Tatsushi