Abstract:
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Recently, many methods have been proposed to test multiple SNPs for the association with a phenotype in a candidate gene or region. To apply these approaches to genome-wide analysis of SNP array or sequencing data, decisions on SNP sets are required. Genes, pathways, and other SNP annotations can be used to construct SNP sets. Also, linkage disequilibrium (LD) information based on the genotype data can be used to construct LD blocks. In this study, we develop a SNP set construction method based on LD block and other biological information. We incorporate the SNP set construction method with the multi-bin linear combination test based on multi-SNP regression and LD clustering. We compared the LD block construction results with the result of Haploview. From the results of HapMap chromosome 22 data, the number of blocks with greater than 70% overlap between the new method and Haploview was about half of the blocks constructed by the new method. There were more singleton blocks with the new method. A simulation study showed that the multi-SNP based test based on newly developed SNP set construction method has a good genome-wide validity and power.
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