Practical Consideration of Genotype Imputation: Sample Size, Window Size, Reference Choice, and Untyped Rate.
Practical Consideration of Genotype Imputation: Sample Size, Window Size, Reference Choice, and Untyped Rate.
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DOI：
10.4310/sii.2011.v4.n3.a8
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发表时间：
2011
影响因子：
0.8
通讯作者：
Liu N
中科院分区：
文献类型：
--
作者：
Zhang B;Zhi D;Zhang K;Gao G;Limdi NN;Liu N
插补提供了一种很有前途的方法来推断遗传研究中缺失和/或未分型的基因型。然而，在实践中，许多因素可能会影响估算的质量。在这项研究中，我们评估了未分型率，研究样本和参考样本的大小，窗口大小和参考选择（混合人群）的影响，作为影响插补质量的因素。结果表明，为了获得良好的插补质量，需要具有小于50%的未分型率、大于50的参考样本大小和大于500个SNP（大约1 MB碱基对）的窗口大小。与全区域插补相比，具有足够大的窗口大小的分段插补提供了改善的功效。对于混合研究样本，如果仅使用外部参考样本组，则应包括代表研究混合人群的祖先人群样本。强烈建议使用内部参考。但是，当内部引用有限时，应谨慎使用外部引用的扩充。更具体地说，从混合物的主要来源人群的样本扩增可以降低插补的质量;扩增与看似遗传无关的队列可能会提高插补的质量。
Imputation offers a promising way to infer the missing and/or untyped genotypes in genetic studies. In practice, however, many factors may affect the quality of imputation. In this study, we evaluated the influence of untyped rate, sizes of the study sample and the reference sample, window size, and reference choice (for admixed population), as the factors affecting the quality of imputation. The results show that in order to obtain good imputation quality, it is necessary to have an untyped rate less than 50%, a reference sample size greater than 50, and a window size of greater than 500 SNPs (roughly 1 MB in base pairs). Compared with the whole-region imputation, piecewise imputation with large-enough window sizes provides improved efficacy. For an admixed study sample, if only an external reference panel is used, it should include samples from the ancestral populations that represent the admixed population under investigation. Internal references are strongly recommended. When internal references are limited, however, augmentation by external references should be used carefully. More specifically, augmentation with samples from the major source populations of the admixture can lower the quality of imputation; augmentation with seemingly genetically unrelated cohorts may improve the quality of imputation.