A Novel Method Combining Linkage Disequilibrium Information and Imputed Functional Knowledge for <i>tag</i>SNP Selection

Analyses of high-density SNPs in genetic studies have the potential problems of prohibitive genotyping costs and inflated false discovery rates. Current methods select subsets of representative SNPs (tagSNPs) using information either on potential biologic functionality of the SNPs or on the underlying linkage disequilibrium (LD) structure, but not both. Combining the two types of information may lead to more effective tagSNP selection. The proposed method combines both functional and LD information using a weighted factor analysis (WFA) model. The WFA was applied to the dense SNP collection from 129 genes sequenced by the SeattleSNPs Program for Genomic Application. TagSNPs selected by WFA were compared with those selected by an LD-based method. WFA allowed prioritization of SNPs that would otherwise share equivalent ranking due to underlying LD structure alone. Furthermore, WFA consistently included SNPs not selected by function or by LD alone. A literature review of a subset of genes revealed that SNPs selected by WFA were more likely represented in published reports.