Linkage disequilibrium analysis of biallelic DNA markers, human quantitative trait loci, and threshold-defined case and control subjects

Linkage disequilibrium (LD) mapping has been applied to many simple, monoge nic, overtly Mendelian human traits, with great success. However, extension s and applications of LD mapping approaches to more complex human quantitat ive 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 fo r individuals likely to possess land not possess) trait-influencing alleles . Simple statistical models for detecting LD between a trait-influencing al lele and neighboring marker alleles are derived that make use of this sampl ing scheme. The power of the proposed method is investigated analytically f or some hypothetical gene-effect scenarios. Our studies indicate that LD ma pping of loci influencing human quantitative trait variation should be poss ible in certain settings. Finally, we consider possible extensions of the p roposed methods, as well as areas for further consideration and improvement .