A Simple and Fast Two-Locus Quality Control Test to Detect False Positives Due to Batch Effects in Genome-Wide Association Studies
A Simple and Fast Two-Locus Quality Control Test to Detect False Positives Due to Batch Effects in Genome-Wide Association Studies
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DOI：
10.1002/gepi.20541
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发表时间：
2010-12-01
影响因子：
2.1
通讯作者：
Visscher, Peter M.
中科院分区：
文献类型：
--
作者：
Lee, Sang Hong;Nyholt, Dale R.;Visscher, Peter M.
通过标准质量控制（QC）的错误基因型的影响在全基因组关联研究、基因型插补以及基于单核苷酸多态性（SNP）的遗传力估计和遗传风险预测中可能是严重的。为了检测这样的基因分型错误，一个简单的两个位点的QC方法，基于单个SNPs和成对的SNPs之间的关联的检验统计量的差异，开发和应用。所提出的方法可以检测到许多有问题的SNP与统计学意义，即使标准的单SNP QC分析未能检测到他们在真实的数据。根据所使用的数据集，未被标准单SNP QC过滤掉但被所提出的方法检测到的错误SNP的数量从几百到几千不等。仿真结果表明，该方法具有较强的鲁棒性，优于已有的其他方法。对于每个SNP 3%的错误率，所提出的方法检测错误基因型的能力类似于80%。这种新的QC方法易于实现，计算效率高，可以为后续的基因型-表型研究提供更好的基因型质量。Genet.流行病学34：854-862，2010. (C)2010 Wiley-Liss，Inc.
The impact of erroneous genotypes having passed standard quality control (QC) can be severe in genome-wide association studies, genotype imputation, and estimation of heritability and prediction of genetic risk based on single nucleotide polymorphisms (SNP). To detect such genotyping errors, a simple two-locus QC method, based on the difference in test statistic of association between single SNPs and pairs of SNPs, was developed and applied. The proposed approach could detect many problematic SNPs with statistical significance even when standard single SNP QC analyses fail to detect them in real data. Depending on the data set used, the number of erroneous SNPs that were not filtered out by standard single SNP QC but detected by the proposed approach varied from a few hundred to thousands. Using simulated data, it was shown that the proposed method was powerful and performed better than other tested existing methods. The power of the proposed approach to detect erroneous genotypes was similar to 80% for a 3% error rate per SNP. This novel QC approach is easy to implement and computationally efficient, and can lead to a better quality of genotypes for subsequent genotype-phenotype investigations. Genet. Epidemiol. 34:854-862, 2010. (C) 2010 Wiley-Liss, Inc.