Tintle Nathan, Gordon Derek, Van Bruggen Dirk, Finch Stephen
Hope College, Department of Mathematics, Holland, Michigan 49423, USA.
Ann Hum Genet. 2009 May;73(Pt 3):370-8. doi: 10.1111/j.1469-1809.2009.00516.x. Epub 2009 Mar 25.
We consider a modification to the traditional genome wide association (GWA) study design: duplicate genotyping. Duplicate genotyping (re-genotyping some of the samples) has long been suggested for quality control reasons; however, it has not been evaluated for its statistical cost-effectiveness. We demonstrate that when genotyping error rates are at least m%, duplicate genotyping provides a cost-effective (more statistical power for the same price) design alternative when relative genotype to phenotype/sample acquisition costs are no more than m%. In addition to cost and error rate, duplicate genotyping is most cost-effective for SNPs with low minor allele frequency. In general, relative genotype to phenotype/sample acquisition costs will be low when following up a limited number of SNPs in the second stage of a two-stage GWA study design, and, thus, duplicate genotyping may be useful in these situations. In cases where many SNPs are being followed up at the second stage, duplicate genotyping only low-quality SNPs with low minor allele frequency may be cost-effective. We also find that in almost all cases where duplicate genotyping is cost-effective, the most cost-effective design strategy involves duplicate genotyping all samples. Free software is provided which evaluates the cost-effectiveness of duplicate genotyping based on user inputs.
我们考虑对传统的全基因组关联（GWA）研究设计进行一项改进：重复基因分型。长期以来，出于质量控制的原因，一直有人建议采用重复基因分型（对部分样本进行重新基因分型）；然而，其统计成本效益尚未得到评估。我们证明，当基因分型错误率至少为m%时，在相对基因型与表型/样本获取成本不超过m%的情况下，重复基因分型可提供一种具有成本效益的（以相同价格获得更大统计效力）设计方案。除了成本和错误率外，重复基因分型对于次要等位基因频率较低的单核苷酸多态性（SNP）最具成本效益。一般来说，在两阶段GWA研究设计的第二阶段对有限数量的SNP进行跟进时，相对基因型与表型/样本获取成本会较低，因此，重复基因分型在这些情况下可能会有用。在第二阶段对许多SNP进行跟进的情况下，仅对次要等位基因频率较低的低质量SNP进行重复基因分型可能具有成本效益。我们还发现，在几乎所有重复基因分型具有成本效益的情况下，最具成本效益的设计策略是对所有样本进行重复基因分型。我们提供了免费软件，可根据用户输入评估重复基因分型的成本效益。
