title: 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: BACKGROUND
  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.
  
  
  METHODS
  VSEAMS is available for download (http://github.com/ollyburren/vseams).
authors.affiliation: 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.
authors.forename: Oliver S
authors.initials: OS
authors.lastname: Burren
authors.affiliation: 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.
authors.forename: Hui
authors.initials: H
authors.lastname: Guo
authors.affiliation: 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.
authors.forename: Chris
authors.initials: C
authors.lastname: Wallace
mesh_terms: D050976:Basic-Leucine Zipper Transcription Factors / Q000235:genetics; D003922:Diabetes Mellitus, Type 1 / Q000235:genetics*; D055106:Genome-Wide Association Study; D006801:Humans; D051740:Ikaros Transcription Factor / Q000235:genetics; D020641:Polymorphism, Single Nucleotide; D011960:Receptors, Estrogen / Q000235:genetics; D018401:Sample Size; D012984:Software; D014157:Transcription Factors / Q000235:genetics*; D000097983:ERRalpha Estrogen-Related Receptor
chemical_list: D050976:Basic-Leucine Zipper Transcription Factors; D051740:Ikaros Transcription Factor; D011960:Receptors, Estrogen; D014157:Transcription Factors; D000097983:ERRalpha Estrogen-Related Receptor; C099359:BATF protein, human; C106285:IKZF3 protein, human