Establishing the role of rare coding variants in known Parkinson's disease risk loci.
Establishing the role of rare coding variants in known Parkinson's disease risk loci.
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DOI：
10.1016/j.neurobiolaging.2017.07.009
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发表时间：
2017-11
影响因子：
4.2
通讯作者：
International Parkinson's Disease Genomics Consortium
中科院分区：
文献类型：
--
作者：
Jansen IE;Gibbs JR;Nalls MA;Price TR;Lubbe S;van Rooij J;Uitterlinden AG;Kraaij R;Williams NM;Brice A;Hardy J;Wood NW;Morris HR;Gasser T;Singleton AB;Heutink P;Sharma M;International Parkinson's Disease Genomics Consortium
已发现许多常见的遗传因素会导致帕金森病的易感性，从而提高我们对相关潜在生物学机制的理解。这些位点中涉及的罕见变异的研究很少。使用国际帕金森病基因组学联盟数据集，我们进行了一项全面的研究，以确定罕见变异对先前发表的 26 个 GWAS 位点对帕金森病的影响。我们应用 Prixfixe 来选择 GWAS 峰下的假定因果基因，这是基于潜在的功能相似性。序列核关联测试用于分析罕见、常见或两种类型变异对 PD 易感性的联合影响。所有基因作为基因组同时测试，每个基因单独测试。我们观察到常见变异的中度关联，证实了我们的遗传数据集中已知的 PD 风险位点的参与。着眼于罕见变异，我们发现了 LRRK2、STBD1 和 SPATA19 的其他关联信号。我们的研究表明，先前确定的 PD GWAS 峰下方的几个假定致病基因中存在罕见变异。
Many common genetic factors have been identified to contribute to PD susceptibility, improving our understanding of the related underlying biological mechanisms. The involvement of rarer variants in these loci have been poorly studied. Using International Parkinson’s Disease Genomics Consortium datasets, we performed a comprehensive study to determine the impact of rare variants in 26 previously published GWAS loci in PD. We applied Prixfixe to select the putative causal genes underneath the GWAS peaks, which was based on underlying functional similarities. The Sequence Kernel Association Test was used to analyze the joint effect of rare, common or both types of variants on PD susceptibility. All genes were tested simultaneously as a gene-set and each gene individually. We observed a moderate association of common variants, confirming the involvement of the known PD risk loci within our genetic datasets. Focusing on rare variants we identified additional association signals for LRRK2, STBD1, and SPATA19. Our study suggests an involvement of rare variants within several putatively causal genes underneath previously identified PD GWAS peaks.
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DOI：
10.1126/science.aaa3650
发表时间：
2015-03-27
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Cirulli ET;Lasseigne BN;Petrovski S;Sapp PC;Dion PA;Leblond CS;Couthouis J;Lu YF;Wang Q;Krueger BJ;Ren Z;Keebler J;Han Y;Levy SE;Boone BE;Wimbish JR;Waite LL;Jones AL;Carulli JP;Day-Williams AG;Staropoli JF;Xin WW;Chesi A;Raphael AR;McKenna-Yasek D;Cady J;Vianney de Jong JM;Kenna KP;Smith BN;Topp S;Miller J;Gkazi A;FALS Sequencing Consortium;Al-Chalabi A;van den Berg LH;Veldink J;Silani V;Ticozzi N;Shaw CE;Baloh RH;Appel S;Simpson E;Lagier-Tourenne C;Pulst SM;Gibson S;Trojanowski JQ;Elman L;McCluskey L;Grossman M;Shneider NA;Chung WK;Ravits JM;Glass JD;Sims KB;Van Deerlin VM;Maniatis T;Hayes SD;Ordureau A;Swarup S;Landers J;Baas F;Allen AS;Bedlack RS;Harper JW;Gitler AD;Rouleau GA;Brown R;Harms MB;Cooper GM;Harris T;Myers RM;Goldstein DB
通讯作者：
Goldstein DB
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
DOI：
10.1016/j.bbrc.2011.08.106
发表时间：
2011-09-30
影响因子：
3.1
作者：
Jiang, Sixin;Wells, Clark D.;Roach, Peter J.
通讯作者：
Roach, Peter J.
影响因子：
5.4
作者：
Klein, Christine;Westenberger, Ana
通讯作者：
Westenberger, Ana
影响因子：
11
作者：
HUGHES, AJ;DANIEL, SE;LEES, AJ
通讯作者：
LEES, AJ