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

Oliver S Burren; Hui Guo; Chris Wallace

doi:10.1093/bioinformatics/btu571

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

Bioinformatics. 2014 Dec 1;30(23):3342-8. doi: 10.1093/bioinformatics/btu571. Epub 2014 Aug 27.

Authors

Oliver S Burren¹, Hui Guo¹, Chris Wallace²

Affiliations

¹ Department of Medical Genetics, JDRF/Wellcome Trust Diabetes and Inflammation Laboratory, NIHR Cambridge Biomedical Research Centre, Cambridge Institute for Medical Research, University of Cambridge, Wellcome Trust/MRC Building, Cambridge Biomedical Campus, Cambridge, CB2 0XY, UK and MRC Biostatistics Unit, Cambridge Institute of Public Health, Forvie Site, Robinson Way, Cambridge Biomedical Campus, Cambridge, CB2 0SR, UK.
² Department of Medical Genetics, JDRF/Wellcome Trust Diabetes and Inflammation Laboratory, NIHR Cambridge Biomedical Research Centre, Cambridge Institute for Medical Research, University of Cambridge, Wellcome Trust/MRC Building, Cambridge Biomedical Campus, Cambridge, CB2 0XY, UK and MRC Biostatistics Unit, Cambridge Institute of Public Health, Forvie Site, Robinson Way, Cambridge Biomedical Campus, Cambridge, CB2 0SR, UK Department of Medical Genetics, JDRF/Wellcome Trust Diabetes and Inflammation Laboratory, NIHR Cambridge Biomedical Research Centre, Cambridge Institute for Medical Research, University of Cambridge, Wellcome Trust/MRC Building, Cambridge Biomedical Campus, Cambridge, CB2 0XY, UK and MRC Biostatistics Unit, Cambridge Institute of Public Health, Forvie Site, Robinson Way, Cambridge Biomedical Campus, Cambridge, CB2 0SR, UK.

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).

Publication types

Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

MeSH terms

Basic-Leucine Zipper Transcription Factors / genetics
Diabetes Mellitus, Type 1 / genetics*
ERRalpha Estrogen-Related Receptor
Genome-Wide Association Study*
Humans
Ikaros Transcription Factor / genetics
Polymorphism, Single Nucleotide
Receptors, Estrogen / genetics
Sample Size
Software*
Transcription Factors / genetics*

Substances

BATF protein, human
Basic-Leucine Zipper Transcription Factors
IKZF3 protein, human
Receptors, Estrogen
Transcription Factors
Ikaros Transcription Factor

Abstract

Publication types

MeSH terms

Substances

Grants and funding