Performance of genotype imputation for rare variants identified in exons and flanking regions of genes.
Performance of genotype imputation for rare variants identified in exons and flanking regions of genes.
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DOI：
10.1371/journal.pone.0024945
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发表时间：
2011
期刊：
影响因子：
3.7
通讯作者：
Ehm MG
中科院分区：
文献类型：
--
作者：
Li L;Li Y;Browning SR;Browning BL;Slater AJ;Kong X;Aponte JL;Mooser VE;Chissoe SL;Whittaker JC;Nelson MR;Ehm MG
与使用实验室技术分析变异相比，基因型插入有可能以更低的成本评估人类遗传变异。罕见变异的归算性能尚未得到全面的研究。我们利用8865份人类样本，对202个基因的外显子和侧翼区域进行高深度重测序，并利用全基因组关联研究（GWAS）数据来表征罕见变异的基因型插补性能。我们评估了从100到3713个受试者的参考集，用于输入Affymetrix （500K和6.0）和Illumina 550K GWAS面板的样品。在3713个个体的参考样本中，可以很好地输入的变异比例（true r2 >.7）为：31% （Illumina 550K）或25% （Affymetrix 500K）的MAF （Minor Allele Frequency）小于或等于0.001,48%或35% (0.001<MAF< = 0.005)， 54%或38% (0.005<MAF< = 0.01)， 78%或57% (0.01<MAF< = 0.05)， 97%或86% （MAF>0.05）。外显子和侧翼区域内常见snp （MAF>0.05）的表现与更均匀分布的snp的估算相当。稀有snp （0.01<MAF< = 0.05）的检测结果更多地依赖于GWAS面板和参考样本的数量。这些结果表明，通过靶向外显子重测序将人类常见变异的评估扩展到具有GWAS数据的其他样本中，常规使用基因型插补，但非常罕见的变异（MAF< = 0.005）的插补将需要数千个受试者的参考小组。
Genotype imputation has the potential to assess human genetic variation at a lower cost than assaying the variants using laboratory techniques. The performance of imputation for rare variants has not been comprehensively studied. We utilized 8865 human samples with high depth resequencing data for the exons and flanking regions of 202 genes and Genome-Wide Association Study (GWAS) data to characterize the performance of genotype imputation for rare variants. We evaluated reference sets ranging from 100 to 3713 subjects for imputing into samples typed for the Affymetrix (500K and 6.0) and Illumina 550K GWAS panels. The proportion of variants that could be well imputed (true r2>0.7) with a reference panel of 3713 individuals was: 31% (Illumina 550K) or 25% (Affymetrix 500K) with MAF (Minor Allele Frequency) less than or equal 0.001, 48% or 35% with 0.001<MAF< = 0.005, 54% or 38% with 0.005<MAF< = 0.01, 78% or 57% with 0.01<MAF< = 0.05, and 97% or 86% with MAF>0.05. The performance for common SNPs (MAF>0.05) within exons and flanking regions is comparable to imputation of more uniformly distributed SNPs. The performance for rare SNPs (0.01<MAF< = 0.05) was much more dependent on the GWAS panel and the number of reference samples. These results suggest routine use of genotype imputation for extending the assessment of common variants identified in humans via targeted exon resequencing into additional samples with GWAS data, but imputation of very rare variants (MAF< = 0.005) will require reference panels with thousands of subjects.
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影响因子：
30.8
作者：
Marchini, Jonathan;Howie, Bryan;Donnelly, Peter
通讯作者：
Donnelly, Peter
COLAUS研究：一项基于人群的研究，旨在研究心血管危险因素和代谢综合征的流行病学和遗传决定因素。
影响因子：
2.1
作者：
Firmann, Mathieu;Mayor, Vladimir;Vidal, Pedro Marques;Bochud, Murielle;Pecoud, Alain;Hayoz, Daniel;Paccaud, Fred;Preisig, Martin;Song, Kijoung S.;Yuan, Xin;Danoff, Theodore M.;Stirnadel, Heide A.;Waterworth, Dawn;Mooser, Vincent;Waeber, Gerard;Vollenweider, Peter
通讯作者：
Vollenweider, Peter
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：
--
作者：
Li, Hao;Wetten, Sally;Roses, Allen D.
通讯作者：
Roses, Allen D.
影响因子：
2.1
作者：
Li, Yun;Willer, Cristen J.;Ding, Jun;Scheet, Paul;Abecasis, Goncalo R.
通讯作者：
Abecasis, Goncalo R.