VSEAMS: a pipeline for variant set enrichment analysis using summary GWAS data identifies IKZF3, BATF and ESRRA as key transcription factors in type 1 diabetes.

Abstract

MOTIVATION: Genome-wide association studies (GWAS) have identified many loci implicated in disease susceptibility. Integration of GWAS summary statistics (P-values) and functional genomic datasets should help to elucidate mechanisms. RESULTS: We extended a non-parametric SNP set enrichment method to test for enrichment of GWAS signals in functionally defined loci to a situation where only GWAS P-values are available. The approach is implemented in VSEAMS, a freely available software pipeline. We use VSEAMS to identify enrichment of type 1 diabetes (T1D) GWAS associations near genes that are targets for the transcription factors IKZF3, BATF and ESRRA. IKZF3 lies in a known T1D susceptibility region, while BATF and ESRRA overlap other immune disease susceptibility regions, validating our approach and suggesting novel avenues of research for T1D. AVAILABILITY AND IMPLEMENTATION: VSEAMS is available for download (http://github.com/ollyburren/vseams).This work was funded by the JDRF (9-2011-253), the Wellcome Trust (091157) and the National Institute for Health Research Cambridge Biomedical Research Centre. The research leading to these results has received funding from the European Unions seventh Framework Programme (FP7/2007-2013) under grant agreement no. 241447 (NAIMIT). The Cambridge Institute for Medical Research is in receipt of a Wellcome Trust Strategic Award (100140). C.W. and H.G. are supported by the Wellcome Trust (089989). ImmunoBase.org is supported by Eli Lilly and Company.This is the final published version, also available from OUP at http://bioinformatics.oxfordjournals.org/content/early/2014/09/18/bioinformatics.btu571.short?rss=1