Sen Saunak, Johannes Frank, Broman Karl W
Department of Epidemiology and Biostatistics, University of California, San Francisco, CA 94143-0560, USA.
Genetics. 2009 Apr;181(4):1613-26. doi: 10.1534/genetics.108.094607. Epub 2009 Jan 19.
Selective genotyping and phenotyping strategies are used to lower the cost of quantitative trait locus studies. Their efficiency has been studied primarily in simplified contexts--when a single locus contributes to the phenotype, and when the residual error (phenotype conditional on the genotype) is normally distributed. It is unclear how these strategies will perform in the context of complex traits where multiple loci, possibly linked or epistatic, may contribute to the trait. We also do not know what genotyping strategies should be used for nonnormally distributed phenotypes. For time-to-event phenotypes there is the additional question of choosing follow-up time duration. We use an information perspective to examine these experimental design issues in the broader context of complex traits and make recommendations on their use.
选择性基因分型和表型分型策略用于降低数量性状基因座研究的成本。其效率主要在简化的背景下进行了研究——当单个基因座影响表型时,以及当残差误差(基于基因型的表型)呈正态分布时。目前尚不清楚这些策略在复杂性状的背景下会如何表现,在复杂性状中,多个基因座(可能连锁或上位)可能会影响该性状。我们也不知道对于非正态分布的表型应该使用何种基因分型策略。对于事件发生时间的表型,还存在选择随访持续时间的额外问题。我们从信息角度在更广泛的复杂性状背景下审视这些实验设计问题,并就其使用提出建议。