title: JEPEG: a summary statistics based tool for gene-level joint testing of functional variants.
abstract: BACKGROUND
  Gene expression is influenced by variants commonly known as expression quantitative trait loci (eQTL). On the basis of this fact, researchers proposed to use eQTL/functional information univariately for prioritizing single nucleotide polymorphisms (SNPs) signals from genome-wide association studies (GWAS). However, most genes are influenced by multiple eQTLs which, thus, jointly affect any downstream phenotype. Therefore, when compared with the univariate prioritization approach, a joint modeling of eQTL action on phenotypes has the potential to substantially increase signal detection power. Nonetheless, a joint eQTL analysis is impeded by (i) not measuring all eQTLs in a gene and/or (ii) lack of access to individual genotypes.
  
  
  RESULTS
  We propose joint effect on phenotype of eQTL/functional SNPs associated with a gene (JEPEG), a novel software tool which uses only GWAS summary statistics to (i) impute the summary statistics at unmeasured eQTLs and (ii) test for the joint effect of all measured and imputed eQTLs in a gene. We illustrate the behavior/performance of the developed tool by analysing the GWAS meta-analysis summary statistics from the Psychiatric Genomics Consortium Stage 1 and the Genetic Consortium for Anorexia Nervosa.
  
  
  CONCLUSIONS
  Applied analyses results suggest that JEPEG complements commonly used univariate GWAS tools by: (i) increasing signal detection power via uncovering (a) novel genes or (b) known associated genes in smaller cohorts and (ii) assisting in fine-mapping of challenging regions, e.g. major histocompatibility complex for schizophrenia.
  
  
  METHODS
  JEPEG, its associated database of eQTL SNPs and usage examples are publicly available at http://code.google.com/p/jepeg/.
  
  
  BACKGROUND
  dlee4@vcu.edu
  
  
  BACKGROUND
  Supplementary data are available at Bioinformatics online.
authors.affiliation: Department of Psychiatry, Virginia Institute for Psychiatric and Behavioral Genetics, Center for Biomarker Research & Personalized Medicine, Virginia Commonwealth University, Richmond, VA 23298, USA and Lieber Institute for Brain Development, Johns Hopkins University, Baltimore, MD 21205, USA.
authors.forename: Donghyung
authors.initials: D
authors.lastname: Lee
authors.affiliation: Department of Psychiatry, Virginia Institute for Psychiatric and Behavioral Genetics, Center for Biomarker Research & Personalized Medicine, Virginia Commonwealth University, Richmond, VA 23298, USA and Lieber Institute for Brain Development, Johns Hopkins University, Baltimore, MD 21205, USA.
authors.forename: Vernell S
authors.initials: VS
authors.lastname: Williamson
authors.affiliation: Department of Psychiatry, Virginia Institute for Psychiatric and Behavioral Genetics, Center for Biomarker Research & Personalized Medicine, Virginia Commonwealth University, Richmond, VA 23298, USA and Lieber Institute for Brain Development, Johns Hopkins University, Baltimore, MD 21205, USA.
authors.forename: T Bernard
authors.initials: TB
authors.lastname: Bigdeli
authors.affiliation: Department of Psychiatry, Virginia Institute for Psychiatric and Behavioral Genetics, Center for Biomarker Research & Personalized Medicine, Virginia Commonwealth University, Richmond, VA 23298, USA and Lieber Institute for Brain Development, Johns Hopkins University, Baltimore, MD 21205, USA.
authors.forename: Brien P
authors.initials: BP
authors.lastname: Riley
authors.affiliation: Department of Psychiatry, Virginia Institute for Psychiatric and Behavioral Genetics, Center for Biomarker Research & Personalized Medicine, Virginia Commonwealth University, Richmond, VA 23298, USA and Lieber Institute for Brain Development, Johns Hopkins University, Baltimore, MD 21205, USA.
authors.forename: Ayman H
authors.initials: AH
authors.lastname: Fanous
authors.affiliation: Department of Psychiatry, Virginia Institute for Psychiatric and Behavioral Genetics, Center for Biomarker Research & Personalized Medicine, Virginia Commonwealth University, Richmond, VA 23298, USA and Lieber Institute for Brain Development, Johns Hopkins University, Baltimore, MD 21205, USA Department of Psychiatry, Virginia Institute for Psychiatric and Behavioral Genetics, Center for Biomarker Research & Personalized Medicine, Virginia Commonwealth University, Richmond, VA 23298, USA and Lieber Institute for Brain Development, Johns Hopkins University, Baltimore, MD 21205, USA Department of Psychiatry, Virginia Institute for Psychiatric and Behavioral Genetics, Center for Biomarker Research & Personalized Medicine, Virginia Commonwealth University, Richmond, VA 23298, USA and Lieber Institute for Brain Development, Johns Hopkins University, Baltimore, MD 21205, USA.
authors.forename: Vladimir I
authors.initials: VI
authors.lastname: Vladimirov
authors.affiliation: Department of Psychiatry, Virginia Institute for Psychiatric and Behavioral Genetics, Center for Biomarker Research & Personalized Medicine, Virginia Commonwealth University, Richmond, VA 23298, USA and Lieber Institute for Brain Development, Johns Hopkins University, Baltimore, MD 21205, USA.
authors.forename: Silviu-Alin
authors.initials: SA
authors.lastname: Bacanu
mesh_terms: D000856:Anorexia Nervosa / Q000235:genetics*; D015415:Biomarkers / Q000032:analysis*; D015331:Cohort Studies; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D055106:Genome-Wide Association Study; D023281:Genomics / Q000379:methods; D005838:Genotype; D006801:Humans; D015201:Meta-Analysis as Topic; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D040641:Quantitative Trait Loci; D012984:Software
chemical_list: D015415:Biomarkers