Schork N J, Nath S K, Fallin D, Chakravarti A
Department of Epidemiology and Biostatistics, Case Western Reserve University, Cleveland, OH 44109, USA.
Am J Hum Genet. 2000 Nov;67(5):1208-18. doi: 10.1086/321201. Epub 2000 Oct 13.
Linkage disequilibrium (LD) mapping has been applied to many simple, monogenic, overtly Mendelian human traits, with great success. However, extensions and applications of LD mapping approaches to more complex human quantitative traits have not been straightforward. In this article, we consider the analysis of biallelic DNA marker loci and human quantitative trait loci in settings that involve sampling individuals from opposite ends of the trait distribution. The purpose of this sampling strategy is to enrich samples for individuals likely to possess (and not possess) trait-influencing alleles. Simple statistical models for detecting LD between a trait-influencing allele and neighboring marker alleles are derived that make use of this sampling scheme. The power of the proposed method is investigated analytically for some hypothetical gene-effect scenarios. Our studies indicate that LD mapping of loci influencing human quantitative trait variation should be possible in certain settings. Finally, we consider possible extensions of the proposed methods, as well as areas for further consideration and improvement.
连锁不平衡（LD）定位已成功应用于许多简单的、单基因的、明显符合孟德尔遗传规律的人类性状。然而，将LD定位方法扩展并应用于更复杂的人类数量性状并非易事。在本文中，我们考虑在从性状分布的两端对个体进行抽样的情况下，对双等位基因DNA标记位点和人类数量性状位点进行分析。这种抽样策略的目的是使样本中富含可能拥有（或不拥有）影响性状等位基因的个体。我们推导了利用这种抽样方案来检测影响性状的等位基因与相邻标记等位基因之间LD的简单统计模型。针对一些假设的基因效应情况，对所提出方法的效能进行了分析研究。我们的研究表明，在某些情况下，对影响人类数量性状变异的位点进行LD定位应该是可行的。最后，我们考虑了所提出方法可能的扩展，以及需要进一步思考和改进的领域。
