Analysis of genome-wide association studies of Alzheimer disease and of Parkinson disease to determine if these 2 diseases share a common genetic risk.
Analysis of genome-wide association studies of Alzheimer disease and of Parkinson disease to determine if these 2 diseases share a common genetic risk.
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DOI：
10.1001/jamaneurol.2013.448
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发表时间：
2013-10
期刊：
影响因子：
29
通讯作者：
IPDGC and GERAD Investigators
中科院分区：
文献类型：
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作者：
Moskvina V;Harold D;Russo G;Vedernikov A;Sharma M;Saad M;Holmans P;Bras JM;Bettella F;Keller MF;Nicolaou N;Simón-Sánchez J;Gibbs JR;Schulte C;Durr A;Guerreiro R;Hernandez D;Brice A;Stefánsson H;Majamaa K;Gasser T;Heutink P;Wood N;Martinez M;Singleton AB;Nalls MA;Hardy J;Owen MJ;O'Donovan MC;Williams J;Morris HR;Williams NM;IPDGC and GERAD Investigators
尽管阿尔茨海默病（AD）和帕金森病（PD）是临床上不同的实体，但存在病理重叠的可能性，一些全基因组关联（GWA）研究表明这2种疾病代表了生物连续统。GWA研究在特发性AD和PD中的应用已经确定了许多含有增加这些疾病风险的遗传变异的基因座。通过检测最近2项PD和AD的GWA研究中是否存在潜在的多效性基因座，评估PD和AD之间的遗传重叠。综合GWA分析。来自英国、德国、法国和美国的数据集。成千上万的AD或PD患者及其对照组。AD和PD的GWA研究的荟萃分析。为了确定可能增加PD和AD风险的多效性等位基因的证据，我们进行了联合PD-AD荟萃分析，并将结果与主要GWA研究中获得的结果进行了比较。我们还测试了潜在的多基因等位基因的净效应，这两种疾病所共有的进行多基因评分分析。最后，我们还进行了一项基于基因的关联分析，旨在检测携带多种致病单核苷酸多态性的基因，其中一些基因会导致PD的风险，而另一些则会导致AD的风险。单核苷酸多态性、多基因和基于基因的分析的详细询问没有发现显著的证据支持存在增加PD和AD风险的基因座。因此，我们的研究结果表明，增加PD和AD风险的基因座并不普遍，病理重叠可能是增加每种疾病风险的主要易感基因的“下游”。
Despite Alzheimer disease (AD) and Parkinson disease (PD) being clinically distinct entities, there is a possibility of a pathological overlap, with some genome-wide association (GWA) studies suggesting that the 2 diseases represent a biological continuum. The application of GWA studies to idiopathic forms of AD and PD have identified a number of loci that contain genetic variants that increase the risk of these disorders. To assess the genetic overlap between PD and AD by testing for the presence of potentially pleiotropic loci in 2 recent GWA studies of PD and AD. Combined GWA analysis. Data sets from the United Kingdom, Germany, France, and the United States. Thousands of patients with AD or PD and their controls. Meta-analysis of GWA studies of AD and PD. To identify evidence for potentially pleiotropic alleles that increased the risk for both PD and AD, we performed a combined PD-AD meta-analysis and compared the results with those obtained in the primary GWA studies. We also tested for a net effect of potentially polygenic alleles that were shared by both disorders by performing a polygenic score analysis. Finally, we also performed a gene-based association analysis that was aimed at detecting genes that harbor multiple disease-causing single-nucleotide polymorphisms, some of which confer a risk of PD and some a risk of AD. Detailed interrogation of the single-nucleotide polymorphism, polygenic, and gene-based analyses resulted in no significant evidence that supported the presence of loci that increase the risk of both PD and AD. Our findings therefore imply that loci that increase the risk of both PD and AD are not widespread and that the pathological overlap could instead be “downstream” of the primary susceptibility genes that increase the risk of each disease.
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影响因子：
9.8
作者：
Lin, Dan-Yu;Sullivan, Patrick F.
通讯作者：
Sullivan, Patrick F.
影响因子：
30.8
作者：
Harold, Denise;Abraham, Richard;Hollingworth, Paul;Sims, Rebecca;Gerrish, Amy;Hamshere, Marian L.;Pahwa, Jaspreet Singh;Moskvina, Valentina;Dowzell, Kimberley;Williams, Amy;Jones, Nicola;Thomas, Charlene;Stretton, Alexandra;Morgan, Angharad R.;Lovestone, Simon;Powell, John;Proitsi, Petroula;Lupton, Michelle K.;Brayne, Carol;Rubinsztein, David C.;Gill, Michael;Lawlor, Brian;Lynch, Aoibhinn;Morgan, Kevin;Brown, Kristelle S.;Passmore, Peter A.;Craig, David;McGuinness, Bernadette;Todd, Stephen;Holmes, Clive;Mann, David;Smith, A. David;Love, Seth;Kehoe, Patrick G.;Hardy, John;Mead, Simon;Fox, Nick;Rossor, Martin;Collinge, John;Maier, Wolfgang;Jessen, Frank;Schuermann, Britta;van den Bussche, Hendrik;Heuser, Isabella;Kornhuber, Johannes;Wiltfang, Jens;Dichgans, Martin;Froelich, Lutz;Hampel, Harald;Huell, Michael;Rujescu, Dan;Goate, Alison M.;Kauwe, John S. K.;Cruchaga, Carlos;Nowotny, Petra;Morris, John C.;Mayo, Kevin;Sleegers, Kristel;Bettens, Karolien;Engelborghs, Sebastiaan;De Deyn, Peter P.;Van Broeckhoven, Christine;Livingston, Gill;Bass, Nicholas J.;Gurling, Hugh;McQuillin, Andrew;Gwilliam, Rhian;Deloukas, Panagiotis;Al-Chalabi, Ammar;Shaw, Christopher E.;Tsolaki, Magda;Singleton, Andrew B.;Guerreiro, Rita;Muehleisen, Thomas W.;Noethen, Markus M.;Moebus, Susanne;Joeckel, Karl-Heinz;Klopp, Norman;Wichmann, H-Erich;Carrasquillo, Minerva M.;Pankratz, V. Shane;Younkin, Steven G.;Holmans, Peter A.;O'Donovan, Michael;Owen, Michael J.;Williams, Julie
通讯作者：
Williams, Julie
影响因子：
30.8
作者：
Satake, Wataru;Nakabayashi, Yuko;Toda, Tatsushi
通讯作者：
Toda, Tatsushi
影响因子：
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作者：
Rocca, Walter A.;Bower, James H.;Maraganore, Demetrius M.
通讯作者：
Maraganore, Demetrius M.
影响因子：
30.8
作者：
通讯作者：
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