An open access database of genome-wide association results.
An open access database of genome-wide association results.
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DOI：
10.1186/1471-2350-10-6
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发表时间：
2009-01-22
影响因子：
--
通讯作者：
O'Donnell CJ
中科院分区：
文献类型：
--
作者：
Johnson AD;O'Donnell CJ
全基因组关联研究的数量正在迅速增长，导致了许多新的疾病位点的发现和复制。结合来自多个GWAS数据集的结果可能会潜在地加强先前的结论，并建议新的疾病位点、途径或多效性基因。然而，目前没有任何数据库或中央资源包含几乎全部的全球气候变化分析结果。我们从118篇GWAS文章中收集了可用的结果，并将其输入到一个包含56,411个重要的SNP-表型关联和伴随信息的数据库中，使该数据库在这里免费可用。在这样做的过程中，我们遇到了一些挑战，并在此描述了建立一个开放的全球气候变化数据库结果的挑战。通过对已有的全球气候变化数据的初步分析和表征，我们展示了通过查询全球气候变化数据来获得新见解的潜力。使用基于基因组Bin的密度分析来搜索基因组的高关联区，以高灵敏度检测出阳性对照基因座(例如，MHC基因座)。同样，对GWA中高度重复的SNPs的分析确定了重复的基因座(如APOE、LPL)。同时，我们确定了新的、高度暗示的各种特征的基因座，这些基因在以前的分析中没有达到全基因组的显著阈值，在某些情况下，得到了初级医学遗传学文献(SLC16A7、CSMD1、OAS1)的大力支持，表明这些基因值得进一步研究。对具有高密度GWAS关联的大多数区域内的连锁不平衡的额外调整并没有实质性地改变我们的发现。拥有一个带有标准化基因注释的中央数据库还允许我们检查功能基因类别(基因本体论)的表示，这些类别包含顶级GWA结果中的一个或多个关联。与细胞黏附功能相关的基因在显著的关联中被高度过度表达(p<；4.6×10-14)，这一发现没有被敏感性分析所干扰。我们提供了一个完整的带有基因注释的Gwas数据库的访问权限，该数据库可用于进一步查询、分析或与其他基因组信息集成。我们做了一些一般性的观察。在已报道的相关SNP中，40%位于RefSeq基因的边界内，68%位于RefSeq基因的60kb以内，这表明在研究结果中倾向于以基因为中心。我们发现，从全球气候分析系统获得的信息具有相当大的异质性，这表明更广泛的社区可以从结果报告的标准化和集中化中受益。
The number of genome-wide association studies (GWAS) is growing rapidly leading to the discovery and replication of many new disease loci. Combining results from multiple GWAS datasets may potentially strengthen previous conclusions and suggest new disease loci, pathways or pleiotropic genes. However, no database or centralized resource currently exists that contains anywhere near the full scope of GWAS results. We collected available results from 118 GWAS articles into a database of 56,411 significant SNP-phenotype associations and accompanying information, making this database freely available here. In doing so, we met and describe here a number of challenges to creating an open access database of GWAS results. Through preliminary analyses and characterization of available GWAS, we demonstrate the potential to gain new insights by querying a database across GWAS. Using a genomic bin-based density analysis to search for highly associated regions of the genome, positive control loci (e.g., MHC loci) were detected with high sensitivity. Likewise, an analysis of highly repeated SNPs across GWAS identified replicated loci (e.g., APOE, LPL). At the same time we identified novel, highly suggestive loci for a variety of traits that did not meet genome-wide significant thresholds in prior analyses, in some cases with strong support from the primary medical genetics literature (SLC16A7, CSMD1, OAS1), suggesting these genes merit further study. Additional adjustment for linkage disequilibrium within most regions with a high density of GWAS associations did not materially alter our findings. Having a centralized database with standardized gene annotation also allowed us to examine the representation of functional gene categories (gene ontologies) containing one or more associations among top GWAS results. Genes relating to cell adhesion functions were highly over-represented among significant associations (p < 4.6 × 10-14), a finding which was not perturbed by a sensitivity analysis. We provide access to a full gene-annotated GWAS database which could be used for further querying, analyses or integration with other genomic information. We make a number of general observations. Of reported associated SNPs, 40% lie within the boundaries of a RefSeq gene and 68% are within 60 kb of one, indicating a bias toward gene-centricity in the findings. We found considerable heterogeneity in information available from GWAS suggesting the wider community could benefit from standardization and centralization of results reporting.
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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：
5.8
作者：
Johnson, Andrew D.;Handsaker, Robert E.;de Bakker, Paul I. W.
通讯作者：
de Bakker, Paul I. W.
从基因组广泛关联研究获得的候选基因结果的务实建议。
影响因子：
2.9
作者：
Curtis, David;Vine, Anna E.;Knight, Jo
通讯作者：
Knight, Jo
影响因子：
4.4
作者：
Kraus, Damian M.;Elliott, Gary S.;Holers, V. Michael
通讯作者：
Holers, V. Michael
影响因子：
3.7
作者：
Dong, Changzheng;Qian, Ziliang;Li, Yixue
通讯作者：
Li, Yixue