title: GREGOR: evaluating global enrichment of trait-associated variants in epigenomic features using a systematic, data-driven approach.
abstract: BACKGROUND
  The majority of variation identified by genome wide association studies falls in non-coding genomic regions and is hypothesized to impact regulatory elements that modulate gene expression. Here we present a statistically rigorous software tool GREGOR (Genomic Regulatory Elements and Gwas Overlap algoRithm) for evaluating enrichment of any set of genetic variants with any set of regulatory features. Using variants from five phenotypes, we describe a data-driven approach to determine the tissue and cell types most relevant to a trait of interest and to identify the subset of regulatory features likely impacted by these variants. Last, we experimentally evaluate six predicted functional variants at six lipid-associated loci and demonstrate significant evidence for allele-specific impact on expression levels. GREGOR systematically evaluates enrichment of genetic variation with the vast collection of regulatory data available to explore novel biological mechanisms of disease and guide us toward the functional variant at trait-associated loci.
  
  
  METHODS
  GREGOR, including source code, documentation, examples, and executables, is available at http://genome.sph.umich.edu/wiki/GREGOR.
  
  
  BACKGROUND
  cristen@umich.edu
  
  
  BACKGROUND
  Supplementary data are available at Bioinformatics online.
authors.affiliation: Department of Computational Medicine and Bioinformatics, University of Michigan, Ann Arbor, MI 48109.
authors.forename: Ellen M
authors.initials: EM
authors.lastname: Schmidt
authors.affiliation: Department of Internal Medicine, Division of Cardiovascular Medicine, University of Michigan, Ann Arbor, MI 48109 and.
authors.forename: Ji
authors.initials: J
authors.lastname: Zhang
authors.affiliation: Department of Computational Medicine and Bioinformatics, University of Michigan, Ann Arbor, MI 48109.
authors.forename: Wei
authors.initials: W
authors.lastname: Zhou
authors.affiliation: Department of Internal Medicine, Division of Cardiovascular Medicine, University of Michigan, Ann Arbor, MI 48109 and.
authors.forename: Jin
authors.initials: J
authors.lastname: Chen
authors.affiliation: Department of Genetics, University of North Carolina, Chapel Hill, NC 27599, USA.
authors.forename: Karen L
authors.initials: KL
authors.lastname: Mohlke
authors.affiliation: Department of Internal Medicine, Division of Cardiovascular Medicine, University of Michigan, Ann Arbor, MI 48109 and.
authors.forename: Y Eugene
authors.initials: YE
authors.lastname: Chen
authors.affiliation: Department of Computational Medicine and Bioinformatics, University of Michigan, Ann Arbor, MI 48109, Department of Internal Medicine, Division of Cardiovascular Medicine, University of Michigan, Ann Arbor, MI 48109 and.
authors.forename: Cristen J
authors.initials: CJ
authors.lastname: Willer
mesh_terms: D000465:Algorithms; D057890:Epigenomics; D014644:Genetic Variation / Q000235:genetics*; D055106:Genome-Wide Association Study; D023281:Genomics / Q000379:methods; D006801:Humans; D009928:Organ Specificity; D010641:Phenotype; D011381:Programming Languages; D040641:Quantitative Trait Loci; D012045:Regulatory Sequences, Nucleic Acid / Q000235:genetics*; D012984:Software