Path: a tool to facilitate pathway-based genetic association analysis

Abstract

Summary: Traditional methods of genetic study design and analysis work well under the scenario that a handful of single nucleotide polymorphisms (SNPs) independently contribute to the risk of disease. For complex diseases, susceptibility may be determined not by a single SNP, but rather a complex interplay between SNPs. For large studies involving hundreds of thousands of SNPs, a brute force search of all possible combinations of SNPs associated with disease is not only inefficient, but also results in a multiple testing paradigm, whereby larger and larger sample sizes are needed to maintain statistical power. Pathway-based methods are an example of one of the many approaches in identifying a subset of SNPs to test for interaction. To help determine which SNP–SNP interactions to test, we developed Path, a software application designed to help researchers interface their data with biological information from several bioinformatics resources. To this end, our application brings together currently available information from nine online bioinformatics resources including the National Center for Biotechnology Information (NCBI), Online Mendelian Inheritance in Man (OMIM), Kyoto Encyclopedia of Genes and Genomes (KEGG), UCSC Genome Browser, Seattle SNPs, PharmGKB, Genetic Association Database, the Single Nucleotide Polymorphism database (dbSNP) and the Innate Immune Database (IIDB).Availability: The software, example datasets and tutorials are freely available from http://genapha.icapture.ubc.ca/PathTutorial.Contact: ddaley@mrl.ubc.ca