Linkage disequilibrium mapping of quantitative trait loci under truncation selection.
As a dense map of single nucleotide polymorphism (SNP) markers are available, population-based linkage disequilibrium (LD) mapping or association study is becoming one of the major tools for identifying quantitative trait loci (QTL) and for fine gene mapping. However, in many cases, LD between the marker and trait locus is not very strong. Approaches that maximize the potential of detecting LD will be essential for the success of LD mapping of QTL. In this paper, we propose two strategies for increasing the probability of detecting LD: (1) phenotypic selection and (2) haplotype LD mapping. To provide the foundations for LD mapping of QTL under selection, we develop analytic tools for assessing the impact of phenotypic selection on allele and haplotype frequencies, and LD under three trait models: single trait locus, two unlinked trait loci, and two linked trait loci with or without epistasis. In addition to a traditional chi(2) test, which compares the difference in allele or haplotype frequencies in the selected sample and population sample, we present multiple regression methods for LD mapping of QTL, and investigate which methods are effective in employing phenotypic selection for QTL mapping. We also develop a statistical framework for investigating and comparing the power of the single marker and multilocus haplotype test for LD mapping of QTL. Finally, the proposed methods are applied to mapping QTL influencing variation in systolic blood pressure in an isolated Chinese population.
Xiong
M
M
Human Genetics Center, University of Texas-Houston, Houston, Tex 77225, USA. mxiong@sph.uth.tmc.edu
Fan
R
R
Jin
L
L
D016009:Chi-Square Distribution; D002874:Chromosome Mapping / Q000379:methods*; D003627:Data Interpretation, Statistical; D006801:Humans; D016014:Linear Models; D015810:Linkage Disequilibrium; D040641:Quantitative Trait Loci