title: JEPEGMIX: gene-level joint analysis of functional SNPs in cosmopolitan cohorts.
abstract: BACKGROUND
  To increase detection power, gene level analysis methods are used to aggregate weak signals. To greatly increase computational efficiency, most methods use as input summary statistics from genome-wide association studies (GWAS). Subsequently, gene statistics are constructed using linkage disequilibrium (LD) patterns from a relevant reference panel. However, all methods, including our own Joint Effect on Phenotype of eQTL/functional single nucleotide polymorphisms (SNPs) associated with a Gene (JEPEG), assume homogeneous panels, e.g. European. However, this renders these tools unsuitable for the analysis of large cosmopolitan cohorts.
  
  
  RESULTS
  We propose a JEPEG extension, JEPEGMIX, which similar to one of our software tools, Direct Imputation of summary STatistics of unmeasured SNPs from MIXed ethnicity cohorts, is capable of estimating accurate LD patterns for cosmopolitan cohorts. JEPEGMIX uses this accurate LD estimates to (i) impute the summary statistics at unmeasured functional variants and (ii) test for the joint effect of all measured and imputed functional variants which are associated with a gene. We illustrate the performance of our tool by analyzing the GWAS meta-analysis summary statistics from the multi-ethnic Psychiatric Genomics Consortium Schizophrenia stage 2 cohort. This practical application supports the immune system being one of the main drivers of the process leading to schizophrenia.
  
  
  METHODS
  Software, annotation database and examples are available at http://dleelab.github.io/jepegmix/.
  
  
  BACKGROUND
  donghyung.lee@vcuhealth.org
  
  
  BACKGROUND
  Supplementary material is available at Bioinformatics online.
authors.affiliation: Department of Psychiatry, Virginia Commonwealth University, Richmond, VA 23298, USA.
authors.forename: Donghyung
authors.initials: D
authors.lastname: Lee
authors.affiliation: Department of Psychiatry, Virginia Commonwealth University, Richmond, VA 23298, USA.
authors.forename: Vernell S
authors.initials: VS
authors.lastname: Williamson
authors.affiliation: Department of Psychiatry, Virginia Commonwealth University, Richmond, VA 23298, USA.
authors.forename: T Bernard
authors.initials: TB
authors.lastname: Bigdeli
authors.affiliation: Department of Psychiatry, Virginia Commonwealth University, Richmond, VA 23298, USA.
authors.forename: Brien P
authors.initials: BP
authors.lastname: Riley
authors.affiliation: Department of Psychiatry, Virginia Commonwealth University, Richmond, VA 23298, USA.
authors.forename: Bradley T
authors.initials: BT
authors.lastname: Webb
authors.affiliation: Department of Psychiatry, Virginia Commonwealth University, Richmond, VA 23298, USA.
authors.forename: Ayman H
authors.initials: AH
authors.lastname: Fanous
authors.affiliation: Department of Psychiatry, Virginia Commonwealth University, Richmond, VA 23298, USA.
authors.forename: Kenneth S
authors.initials: KS
authors.lastname: Kendler
authors.affiliation: Department of Psychiatry, Virginia Commonwealth University, Richmond, VA 23298, USA.
authors.forename: Vladimir I
authors.initials: VI
authors.lastname: Vladimirov
authors.affiliation: Department of Psychiatry, Virginia Commonwealth University, Richmond, VA 23298, USA.
authors.forename: Silviu-Alin
authors.initials: SA
authors.lastname: Bacanu
mesh_terms: D015331:Cohort Studies; D005006:Ethnicity / Q000235:genetics*; D005820:Genetic Testing; D005828:Genetics, Population; D055106:Genome-Wide Association Study / Q000379:methods; D023281:Genomics / Q000379:methods; D006801:Humans; D015810:Linkage Disequilibrium; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D012559:Schizophrenia / Q000235:genetics*; D012984:Software