Fast and accurate genotype imputation in genome-wide association studies through pre-phasing.
Fast and accurate genotype imputation in genome-wide association studies through pre-phasing.
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DOI：
10.1038/ng.2354
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发表时间：
2012-07-22
期刊：
影响因子：
30.8
通讯作者：
Abecasis, Goncalo R.
中科院分区：
文献类型：
--
作者：
Howie, Bryan;Fuchsberger, Christian;Stephens, Matthew;Marchini, Jonathan;Abecasis, Goncalo R.
测序工作，包括1000基因组计划和疾病特异性工作，正在产生大量的单倍型，可用于全基因组关联研究（GWAS）的基因型植入。从这些参考面板进行推算可以帮助识别新的风险等位基因，但是在现有方法中使用大型面板会带来很高的计算负担。为了使估算更容易获得，我们引入了一种称为“预相位”的策略，该策略在保持领先方法的准确性的同时，将计算成本降低了几个数量级。简而言之，我们首先统计估计每个GWAS个体的单倍型（“前期”），然后将缺失的基因型输入到这些估计的单倍型中。这减少了计算成本，因为：(i) GWAS样本必须只分阶段一次，而标准方法将隐式地随着每次参考面板更新而重新分阶段；（ii）将一个分阶段的GWAS基因型与一个参考单倍型匹配比将未分阶段的GWAS基因型与一对参考单倍型匹配要快得多。随着参考面板的发展，这种策略对于重复输入将特别有价值。
Sequencing efforts, including the 1000 Genomes Project and disease-specific efforts, are producing large collections of haplotypes that can be used for genotype imputation in genome-wide association studies (GWAS). Imputing from these reference panels can help identify new risk alleles, but the use of large panels with existing methods imposes a high computational burden. To keep imputation broadly accessible, we introduce a strategy called “pre-phasing” that maintains the accuracy of leading methods while cutting computational costs by orders of magnitude. In brief, we first statistically estimate the haplotypes for each GWAS individual (“pre-phasing”) and then impute missing genotypes into these estimated haplotypes. This reduces the computational cost because: (i) the GWAS samples must be phased only once, whereas standard methods would implicitly re-phase with each reference panel update; (ii) it is much faster to match a phased GWAS haplotype to one reference haplotype than to match unphased GWAS genotypes to a pair of reference haplotypes. This strategy will be particularly valuable for repeated imputation as reference panels evolve.
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影响因子：
30.8
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Nair RP;Duffin KC;Helms C;Ding J;Stuart PE;Goldgar D;Gudjonsson JE;Li Y;Tejasvi T;Feng BJ;Ruether A;Schreiber S;Weichenthal M;Gladman D;Rahman P;Schrodi SJ;Prahalad S;Guthery SL;Fischer J;Liao W;Kwok PY;Menter A;Lathrop GM;Wise CA;Begovich AB;Voorhees JJ;Elder JT;Krueger GG;Bowcock AM;Abecasis GR;Collaborative Association Study of Psoriasis
通讯作者：
Collaborative Association Study of Psoriasis
影响因子：
30.8
作者：
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通讯作者：
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影响因子：
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作者：
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通讯作者：
Abecasis, Goncalo R.
影响因子：
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作者：
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通讯作者：
Cheung, Vivian G.
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.