Linkage disequilibrium analysis of biallelic DNA markers, human quantitative trait loci, and threshold-defined case and control subjects.
Case-Control-Studies, Chromosome-Mapping, Computer-Simulation, Gene-Frequency, Genes-Dominant, Genes-Recessive, Genetic-Markers, Haplotypes, Human, Linkage-Disequilibrium, Models-Genetic, Quantitative-Trait, Sample-Size, Software, SUPPORT-U-S-GOVT-P-H-S
Am J Hum Genet 2000 Nov; 67(5):1208-18.
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.
Schork, N J.; Nath, S K.; Fallin, D; and Chakravarti, A, " Linkage disequilibrium analysis of biallelic DNA markers, human quantitative trait loci, and threshold-defined case and control subjects." (2000). Faculty Research 2000 - 2009. 149.
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