Pathway-based analysis in genome-wide association study (GWAS) is being widely used to uncover novel multi-genic functional associations. Many of these pathway-based methods have been used to test the enrichment of the associated genes in the pathways, but exhibited low powers and were highly affected by free parameters. We present the novel method and software GSA-SNP2 for pathway enrichment analysis of GWAS P-value data. GSA-SNP2 provides high power, decent type I error control and fast computation by incorporating the random set model and SNP-count adjusted gene score. In a comparative study using simulated and real GWAS data, GSA-SNP2 exhibited high power and best prioritized gold standard positive pathways compared with six existing enrichment-based methods and two self-contained methods (alternative pathway analysis approach). Based on these results, the difference between pathway analysis approaches was investigated and the effects of the gene correlation structures on the pathway enrichment analysis were also discussed. In addition, GSA-SNP2 is able to visualize protein interaction networks within and across the significant pathways so that the user can prioritize the core subnetworks for further studies. GSA-SNP2 is freely available at https://sourceforge.net/projects/gsasnp2.
Pubmed ID: 29562348 RIS Download
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Consortium of researchers aiming to characterize the genetic basis of type 2 diabetes with a principal focus on samples of European descent. DIAGRAM also features a database of DIAGRAM publications and diabetes-related research data.
View all literature mentionsA computational tool that tests for enrichment of genetic associations in predefined biological processes or sets of functionally related genes, using genome-wide genetic data as input.
View all literature mentionsA tool for the gene-set (or pathway) analysis of a genome-wide association study result. It accepts a genome-wide list of SNPs and their association P-values. It summarizes the SNP P-values into nearby genes. The gene-by-gene summary results are then further summarized by gene-sets such as Gene Ontology, KEGG pathways, or user-created gene-sets. Various standardization and statistical tests can be performed and the resulting gene-sets that pass a significance level after multiple-testing correction are reported. The tool is written in Java and is available as a standalone version.
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