JSM 2004 - Toronto

Abstract #300898

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Activity Number: 310
Type: Contributed
Date/Time: Wednesday, August 11, 2004 : 8:30 AM to 10:20 AM
Sponsor: Biometrics Section
Abstract - #300898
Title: Efficient Study Designs for Identifying SNPs Responsible for a Linkage Signal
Author(s): Mingyao Li*+ and Goncalo Abecasis and Michael Boehnke
Companies: University of Michigan and University of Michigan and University of Michigan
Address: 1420 Washington Heights, Ann Arbor, MI, 48109,
Keywords: linkage disequilibrium ; gene localization ; identification of disease genes ; mapping complex traits
Abstract:

Once genetic linkage has been identified for a complex disease, the next step is often association analysis, in which single-nucleotide polymorphisms (SNPs) within the linkage region are genotyped and tested for association with the disease. If a SNP shows evidence for association, a key question is to what degree the linkage result can be explained by the associated SNP. To answer this question, we developed a novel statistical method that quantifies the degree of linkage disequilibrium (LD) between the associated SNP and the putative disease locus. We summarized the available data by a simple parametric likelihood of the marker data conditional on the trait data based on disease penetrances and disease-SNP haplotype frequencies, and we proposed two likelihood ratio tests to distinguish the relationship between the associated SNP and the putative disease locus. We further compared different study designs for testing whether the SNP is responsible for a linkage signal. To investigate the performance of our method, we performed simulation studies.

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