title: Performance Comparison of Two Gene Set Analysis Methods for Genome-wide Association Study Results: GSA-SNP vs i-GSEA4GWAS.
abstract: Gene set analysis (GSA) is useful in interpreting a genome-wide association study (GWAS) result in terms of biological mechanism. We compared the performance of two different GSA implementations that accept GWAS p-values of single nucleotide polymorphisms (SNPs) or gene-by-gene summaries thereof, GSA-SNP and i-GSEA4GWAS, under the same settings of inputs and parameters. GSA runs were made with two sets of p-values from a Korean type 2 diabetes mellitus GWAS study: 259,188 and 1,152,947 SNPs of the original and imputed genotype datasets, respectively. When Gene Ontology terms were used as gene sets, i-GSEA4GWAS produced 283 and 1,070 hits for the unimputed and imputed datasets, respectively. On the other hand, GSA-SNP reported 94 and 38 hits, respectively, for both datasets. Similar, but to a lesser degree, trends were observed with Kyoto Encyclopedia of Genes and Genomes (KEGG) gene sets as well. The huge number of hits by i-GSEA4GWAS for the imputed dataset was probably an artifact due to the scaling step in the algorithm. The decrease in hits by GSA-SNP for the imputed dataset may be due to the fact that it relies on Z-statistics, which is sensitive to variations in the background level of associations. Judicious evaluation of the GSA outcomes, perhaps based on multiple programs, is recommended.
authors.affiliation: Department of Bioinformatics and Life Science, Soongsil University, Seoul 156-743, Korea.
authors.forename: Ji-Sun
authors.initials: JS
authors.lastname: Kwon
authors.forename: Jihye
authors.initials: J
authors.lastname: Kim
authors.forename: Dougu
authors.initials: D
authors.lastname: Nam
authors.forename: Sangsoo
authors.initials: S
authors.lastname: Kim
keywords: GSA-SNP; gene set analysis; genome-wide association study; i-GSEA4GWAS; imputation