JSM 2005 - Toronto

Abstract #303855

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Activity Number: 63
Type: Contributed
Date/Time: Sunday, August 7, 2005 : 4:00 PM to 5:50 PM
Sponsor: Biometrics Section
Abstract - #303855
Title: Multilocus LD Measure and Tagging SNP Selection with Generalized Mutual Information
Author(s): Zhenqiu Liu*+ and Shili Lin
Companies: The Ohio State University and The Ohio State University
Address: Department of Statistics, Columbus, OH, 43210, United States
Keywords: Kullback-Leibler distance ; entropy ; haplotype diversity ; linkage disequilibrium ; single nucleotide polymorphism (SNP) ; haplotype block
Abstract:

Linkage disequilibrium (LD) plays a central role in fine mapping of disease genes and in characterizing haplotype blocks. Classical LD measures often are used to study the relationship between two loci. Based on such pairwise measures, haplotype block detection and tag SNP selection algorithms have been devised. Although successful in many applications, the pairwise nature of such measures does not provide a direct characterization of joint LD among multiple loci. We propose a multilocus LD measure based on Kullback-Leibler distance. This measure seeks to quantify the distance between an observed haplotype distribution and the expected one assuming linkage equilibrium. Based on this multilocus LD measure and an entropy measure that characterizes haplotype diversity (HD), we introduce a stepwise tag SNP selection algorithm. This represents a unified approach for SNP selection in that it takes into account both the HD and LD objectives. Applications to both simulated and real data demonstrate the utility of the methods for handling a large number of SNPs, indicate that multilocus LD patterns can be captured well, and show informative and nonredundant SNPs can be selected effectively.

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