Large-scale meta-analysis of genome-wide association data identifies six new risk loci for Parkinson's disease.
Large-scale meta-analysis of genome-wide association data identifies six new risk loci for Parkinson's disease.
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DOI：
10.1038/ng.3043
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发表时间：
2014-09
期刊：
影响因子：
30.8
通讯作者：
Singleton, Andrew B.
中科院分区：
文献类型：
--
作者：
Nalls, Mike A.;Pankratz, Nathan;Lill, Christina M.;Do, Chuong B.;Hernandez, Dena G.;Saad, Mohamad;DeStefano, Anita L.;Kara, Eleanna;Bras, Jose;Sharma, Manu;Schulte, Claudia;Keller, Margaux F.;Arepalli, Sampath;Letson, Christopher;Edsall, Connor;Stefansson, Hreinn;Liu, Xinmin;Pliner, Hannah;Lee, Joseph H.;Cheng, Rong;Ikram, M. Arfan;Ioannidis, John P. A.;Hadjigeorgiou, Georgios M.;Bis, Joshua C.;Martinez, Maria;Perlmutter, Joel S.;Goate, Alison;Marder, Karen;Fiske, Brian;Sutherland, Margaret;Xiromerisiou, Georgia;Myers, Richard H.;Clark, Lorraine N.;Stefansson, Kari;Hardy, John A.;Heutink, Peter;Chen, Honglei;Wood, Nicholas W.;Houlden, Henry;Payami, Haydeh;Brice, Alexis;Scott, William K.;Gasser, Thomas;Bertram, Lars;Eriksson, Nicholas;Foroud, Tatiana;Singleton, Andrew B.
我们对帕金森病全基因组关联研究进行了Meta分析，使用了13，708例病例和95，282例对照中的7，893，274种常见变异。26个基因座被确定为全基因组显著的;然后在一组独立的5，353例病例和5，551例对照中对这些和先前报道的另外6个基因座进行了测试。在检测的32个SNP中，有24个重复，包括6个新位点。基因座内条件分析显示GBA、GAK/DGKQ、SNCA和HLA等4个基因座含有次要独立危险变异。我们总共在24个基因座上识别并复制了28个帕金森病的独立风险变异。虽然每个基因座的影响很小，但风险特征分析显示，在遗传风险的最高和最低五分位数的比较中，累积风险很大（OR=3.31，95% CI：2.55，4.30; p值= 2×10−16）。我们还发现了6个与近端基因表达或DNA甲基化相关的风险位点。
We conducted a meta analysis of Parkinson’s disease genome-wide association studies using a common set of 7,893,274 variants across 13,708 cases and 95,282 controls. Twenty-six loci were identified as genome-wide significant; these and six additional previously reported loci were then tested in an independent set of 5,353 cases and 5,551 controls. Of the 32 tested SNPs, 24 replicated, including 6 novel loci. Conditional analyses within loci show four loci including GBA, GAK/DGKQ, SNCA, and HLA contain a secondary independent risk variant. In total we identified and replicated 28 independent risk variants for Parkinson disease across 24 loci. While the effect of each individual locus is small, a risk profile analysis revealed a substantial cummulative risk in a comparison highest versus lowest quintiles of genetic risk (OR=3.31, 95% CI: 2.55, 4.30; p-value = 2×10−16). We also show 6 risk loci associated with proximal gene expression or DNA methylation.
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影响因子：
4.5
作者：
Do CB;Tung JY;Dorfman E;Kiefer AK;Drabant EM;Francke U;Mountain JL;Goldman SM;Tanner CM;Langston JW;Wojcicki A;Eriksson N
通讯作者：
Eriksson N
影响因子：
3.7
作者：
Hernandez DG;Nalls MA;Ylikotila P;Keller M;Hardy JA;Majamaa K;Singleton AB
通讯作者：
Singleton AB
影响因子：
30.8
作者：
Satake, Wataru;Nakabayashi, Yuko;Toda, Tatsushi
通讯作者：
Toda, Tatsushi
DOI：
10.1161/circgenetics.108.829747
发表时间：
2009-02
期刊：
Circulation. Cardiovascular genetics
影响因子：
--
作者：
Psaty BM;O'Donnell CJ;Gudnason V;Lunetta KL;Folsom AR;Rotter JI;Uitterlinden AG;Harris TB;Witteman JC;Boerwinkle E;CHARGE Consortium
通讯作者：
CHARGE Consortium
影响因子：
3.5
作者：
de Bakker, Paul I. W.;Ferreira, Manuel A. R.;Voight, Benjamin F.
通讯作者：
Voight, Benjamin F.