A generic coalescent-based framework for the selection of a reference panel for imputation.
A generic coalescent-based framework for the selection of a reference panel for imputation.
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DOI：
10.1002/gepi.20505
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发表时间：
2010-12
影响因子：
2.1
通讯作者：
Halperin, Eran
中科院分区：
文献类型：
--
作者：
Pasaniuc, Bogdan;Avinery, Ram;Gur, Tom;Skibola, Christine F.;Bracci, Paige M.;Halperin, Eran
全基因组关联研究分析的一个重要组成部分涉及未在研究样本中直接测量的基因型的归算。代入程序使用群体中的连锁不平衡（LD）结构来推断未观察到的单核苷酸多态性的基因型。LD结构通常是从与所研究群体相匹配的参考群体的密集基因型图中了解到的。在许多情况下，没有与所研究的人口完全匹配的参考人口，自然就产生了如何选择用于估算的参考人口的问题。在这里，我们提出了一个基于coalescent的方法来解决这个问题。与目前的归算方法相比，我们的方法为研究人群中的每个样本和基因组中的每个区域分配了不同的参考数据集。这样就可以灵活地解释种群内部和种群之间的多样性。此外，由于我们的方法分别处理基因组中的每个区域，因此我们的方法适用于最近混合种群的归算。我们在大量人群中评估了我们的方法，发现我们选择的参考数据集大大提高了代入的准确性，特别是对于低LD地区和没有参考人口的人群以及混合人群（如西班牙裔人口）。我们的方法是通用的，可以潜在地作为一个附加组件纳入任何可用的插补方法。
An important component in the analysis of genome-wide association studies involves the imputation of genotypes that have not been measured directly in the studied samples. The imputation procedure uses the linkage disequilibrium (LD) structure in the population to infer the genotype of an unobserved single nucleotide polymorphism. The LD structure is normally learned from a dense genotype map of a reference population that matches the studied population. In many instances there is no reference population that exactly matches the studied population, and a natural question arises as to how to choose the reference population for the imputation. Here we present a Coalescent-based method that addresses this issue. In contrast to the current paradigm of imputation methods, our method assigns a different reference dataset for each sample in the studied population, and for each region in the genome. This allows the flexibility to account for the diversity within populations, as well as across populations. Furthermore, because our approach treats each region in the genome separately, our method is suitable for the imputation of recently admixed populations. We evaluated our method across a large set of populations and found that our choice of reference data set considerably improves the accuracy of imputation, especially for regions with low LD and for populations without a reference population available as well as for admixed populations such as the Hispanic population. Our method is generic and can potentially be incorporated in any of the available imputation methods as an add-on.
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影响因子：
30.8
作者：
Marchini, Jonathan;Howie, Bryan;Donnelly, Peter
通讯作者：
Donnelly, Peter
影响因子：
30.8
作者：
Zeggini, Eleftheria;Scott, Laura J.;Saxena, Richa;Voight, Benjamin F.;Marchini, Jonathan L.;Hu, Tianle;de Bakker, Paul I. W.;Abecasis, Goncalo R.;Almgren, Peter;Andersen, Gitte;Ardlie, Kristin;Bostroem, Kristina Bengtsson;Bergman, Richard N.;Bonnycastle, Lori L.;Borch-Johnsen, Knut;Burtt, Noel P.;Chen, Hong;Chines, Peter S.;Daly, Mark J.;Deodhar, Parimal;Ding, Chia-Jen;Doney, Alex S. F.;Duren, William L.;Elliott, Katherine S.;Erdos, Michael R.;Frayling, Timothy M.;Freathy, Rachel M.;Gianniny, Lauren;Grallert, Harald;Grarup, Niels;Groves, Christopher J.;Guiducci, Candace;Hansen, Torben;Herder, Christian;Hitman, Graham A.;Hughes, Thomas E.;Isomaa, Bo;Jackson, Anne U.;Jorgensen, Torben;Kong, Augustine;Kubalanza, Kari;Kuruvilla, Finny G.;Kuusisto, Johanna;Langenberg, Claudia;Lango, Hana;Lauritzen, Torsten;Li, Yun;Lindgren, Cecilia M.;Lyssenko, Valeriya;Marvelle, Amanda F.;Meisinger, Christa;Midthjell, Kristian;Mohlke, Karen L.;Morken, Mario A.;Morris, Andrew D.;Narisu, Narisu;Nilsson, Peter;Owen, Katharine R.;Palmer, Colin N. A.;Payne, Felicity;Perry, John R. B.;Pettersen, Elin;Platou, Carl;Prokopenko, Inga;Qi, Lu;Qin, Li;Rayner, Nigel W.;Rees, Matthew;Roix, Jeffrey J.;Sandbaek, Anelli;Shields, Beverley;Sjogren, Marketa;Steinthorsdottir, Valgerdur;Stringham, Heather M.;Swift, Amy J.;Thorleifsson, Gudmar;Thorsteinsdottir, Unnur;Timpson, Nicholas J.;Tuomi, Tiinamaija;Tuomilehto, Jaakko;Walker, Mark;Watanabe, Richard M.;Weedon, Michael N.;Willer, Cristen J.;Illig, Thomas;Hveem, Kristian;Hu, Frank B.;Laakso, Markku;Stefansson, Kari;Pedersen, Oluf;Wareham, Nicholas J.;Barroso, Ines;Hattersley, Andrew T.;Collins, Francis S.;Groop, Leif;McCarthy, Mark I.;Boehnke, Michael;Altshuler, David
通讯作者：
Altshuler, David
影响因子：
9.8
作者：
Huang, Lucy;Wang, Chaolong;Rosenberg, Noah A.
通讯作者：
Rosenberg, Noah A.
DOI：
10.1098/rstb.1995.0086
发表时间：
1995-07-29
影响因子：
6.3
作者：
HUDSON, RR;KAPLAN, NL
通讯作者：
KAPLAN, NL
用于下一代全基因组关联研究的灵活而准确的基因型插补方法。
影响因子：
4.5
作者：
Howie, Bryan N.;Donnelly, Peter;Marchini, Jonathan
通讯作者：
Marchini, Jonathan