Genetics of Alzheimer disease in the pre- and post-GWAS era.
Genetics of Alzheimer disease in the pre- and post-GWAS era.
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DOI：
10.1186/alzrt26
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发表时间：
2010-03-05
期刊：
影响因子：
--
通讯作者：
Ertekin-Taner N
中科院分区：
文献类型：
--
作者：
Ertekin-Taner N
自20世纪90年代以来，阿尔茨海默病（AD）的遗传学一直是一个活跃的研究领域。确定性突变的APP，PSEN1和PSEN2基因负责早发性常染色体显性遗传的AD家族形式的鉴定导致更好地了解这种疾病的病理生理。在过去的十年中，从遗传连锁和小规模关联研究中出现的大量候选基因和区域产生了有趣的“命中”，这些命中通常被证明难以持续复制。在过去两年中，11项已发表的AD全基因组关联研究（GWAS）证实了APOE作为迟发型AD遗传危险因素的普遍公认作用，并产生了需要确认的其他候选基因。目前尚不清楚GWAS尽管是复杂疾病遗传学中一种有前途的新方法，但是否可以帮助解释AD的大部分潜在遗传风险。这篇综述简要总结了GWAS时代之前AD的遗传学研究，主要集中在最近GWAS的发现。潜在的方法，可以提供进一步深入了解AD的遗传学在后GWAS时代进行了讨论。
Since the 1990s, the genetics of Alzheimer disease (AD) has been an active area of research. The identification of deterministic mutations in the APP, PSEN1, and PSEN2 genes responsible for early-onset autosomal dominant familial forms of AD led to a better understanding of the pathophysiology of this disease. In the past decade, the plethora of candidate genes and regions emerging from genetic linkage and smaller-scale association studies yielded intriguing 'hits' that have often proven difficult to replicate consistently. In the last two years, 11 published genome-wide association studies (GWASs) in AD confirmed the universally accepted role of APOE as a genetic risk factor for late-onset AD as well as generating additional candidate genes that require confirmation. It is unclear whether GWASs, though a promising novel approach in the genetics of complex diseases, can help explain most of the underlying genetic risk for AD. This review provides a brief summary of the genetic studies in AD preceding the GWAS era, with the main focus on the findings from recent GWASs. Potential approaches that could provide further insight into the genetics of AD in the post-GWAS era are also discussed.
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影响因子：
64.8
作者：
Frazer, Kelly A.;Ballinger, Dennis G.;Cox, David R.;Hinds, David A.;Stuve, Laura L.;Gibbs, Richard A.;Belmont, John W.;Boudreau, Andrew;Hardenbol, Paul;Leal, Suzanne M.;Pasternak, Shiran;Wheeler, David A.;Willis, Thomas D.;Yu, Fuli;Yang, Huanming;Zeng, Changqing;Gao, Yang;Hu, Haoran;Hu, Weitao;Li, Chaohua;Lin, Wei;Liu, Siqi;Pan, Hao;Tang, Xiaoli;Wang, Jian;Wang, Wei;Yu, Jun;Zhang, Bo;Zhang, Qingrun;Zhao, Hongbin;Zhao, Hui;Zhou, Jun;Gabriel, Stacey B.;Barry, Rachel;Blumenstiel, Brendan;Camargo, Amy;Defelice, Matthew;Faggart, Maura;Goyette, Mary;Gupta, Supriya;Moore, Jamie;Nguyen, Huy;Onofrio, Robert C.;Parkin, Melissa;Roy, Jessica;Stahl, Erich;Winchester, Ellen;Ziaugra, Liuda;Altshuler, David;Shen, Yan;Yao, Zhijian;Huang, Wei;Chu, Xun;He, Yungang;Jin, Li;Liu, Yangfan;Shen, Yayun;Sun, Weiwei;Wang, Haifeng;Wang, Yi;Wang, Ying;Xiong, Xiaoyan;Xu, Liang;Waye, Mary M. Y.;Tsui, Stephen K. W.;Wong, J. Tze-Fei;Galver, Luana M.;Fan, Jian-Bing;Gunderson, Kevin;Murray, Sarah S.;Oliphant, Arnold R.;Chee, Mark S.;Montpetit, Alexandre;Chagnon, Fanny;Ferretti, Vincent;Leboeuf, Martin;Olivier, Jean-Franccois;Phillips, Michael S.;Roumy, Stephanie;Sallee, Clementine;Verner, Andrei;Hudson, Thomas J.;Kwok, Pui-Yan;Cai, Dongmei;Koboldt, Daniel C.;Miller, Raymond D.;Pawlikowska, Ludmila;Taillon-Miller, Patricia;Xiao, Ming;Tsui, Lap-Chee;Mak, William;Song, You Qiang;Tam, Paul K. H.;Nakamura, Yusuke;Kawaguchi, Takahisa;Kitamoto, Takuya;Morizono, Takashi;Nagashima, Atsushi;Ohnishi, Yozo;Sekine, Akihiro;Tanaka, Toshihiro;Tsunoda, Tatsuhiko;Deloukas, Panos;Bird, Christine P.;Delgado, Marcos;Dermitzakis, Emmanouil T.;Gwilliam, Rhian;Hunt, Sarah;Morrison, Jonathan;Powell, Don;Stranger, Barbara E.;Whittaker, Pamela;Bentley, David R.;Daly, Mark J.;de Bakker, Paul I. W.;Barrett, Jeff;Chretien, Yves R.;Maller, Julian;McCarroll, Steve;Patterson, Nick;Pe'er, Itsik;Price, Alkes;Purcell, Shaun;Richter, Daniel J.;Sabeti, Pardis;Saxena, Richa;Schaffner, Stephen F.;Sham, Pak C.;Varilly, Patrick;Altshuler, David;Stein, Lincoln D.;Krishnan, Lalitha;Smith, Albert Vernon;Tello-Ruiz, Marcela K.;Thorisson, Gudmundur A.;Chakravarti, Aravinda;Chen, Peter E.;Cutler, David J.;Kashuk, Carl S.;Lin, Shin;Abecasis, Goncalo R.;Guan, Weihua;Li, Yun;Munro, Heather M.;Qin, Zhaohui Steve;Thomas, Daryl J.;McVean, Gilean;Auton, Adam;Bottolo, Leonardo;Cardin, Niall;Eyheramendy, Susana;Freeman, Colin;Marchini, Jonathan;Myers, Simon;Spencer, Chris;Stephens, Matthew;Donnelly, Peter;Cardon, Lon R.;Clarke, Geraldine;Evans, David M.;Morris, Andrew P.;Weir, Bruce S.;Tsunoda, Tatsuhiko;Johnson, Todd A.;Mullikin, James C.;Sherry, Stephen T.;Feolo, Michael;Skol, Andrew
通讯作者：
Skol, Andrew
影响因子：
2.7
作者：
Abraham R;Moskvina V;Sims R;Hollingworth P;Morgan A;Georgieva L;Dowzell K;Cichon S;Hillmer AM;O'Donovan MC;Williams J;Owen MJ;Kirov G
通讯作者：
Kirov G
影响因子：
64.8
作者：
Duff, K;Eckman, C;Younkin, S
通讯作者：
Younkin, S
影响因子：
9.8
作者：
Bertram, Lars;Lange, Christoph;Tanzi, Rudolph E.
通讯作者：
Tanzi, Rudolph E.
影响因子：
9.8
作者：
Daw, EW;Payami, H;Wijsman, EM
通讯作者：
Wijsman, EM