title: DISTMIX: direct imputation of summary statistics for unmeasured SNPs from mixed ethnicity cohorts.
abstract: BACKGROUND
  To increase the signal resolution for large-scale meta-analyses of genome-wide association studies, genotypes at unmeasured single nucleotide polymorphisms (SNPs) are commonly imputed using large multi-ethnic reference panels. However, the ever increasing size and ethnic diversity of both reference panels and cohorts makes genotype imputation computationally challenging for moderately sized computer clusters. Moreover, genotype imputation requires subject-level genetic data, which unlike summary statistics provided by virtually all studies, is not publicly available. While there are much less demanding methods which avoid the genotype imputation step by directly imputing SNP statistics, e.g. Directly Imputing summary STatistics (DIST) proposed by our group, their implicit assumptions make them applicable only to ethnically homogeneous cohorts.
  
  
  RESULTS
  To decrease computational and access requirements for the analysis of cosmopolitan cohorts, we propose DISTMIX, which extends DIST capabilities to the analysis of mixed ethnicity cohorts. The method uses a relevant reference panel to directly impute unmeasured SNP statistics based only on statistics at measured SNPs and estimated/user-specified ethnic proportions. Simulations show that the proposed method adequately controls the Type I error rates. The 1000 Genomes panel imputation of summary statistics from the ethnically diverse Psychiatric Genetic Consortium Schizophrenia Phase 2 suggests that, when compared to genotype imputation methods, DISTMIX offers comparable imputation accuracy for only a fraction of computational resources.
  
  
  METHODS
  DISTMIX software, its reference population data, and usage examples are publicly available at http://code.google.com/p/distmix.
  
  
  BACKGROUND
  dlee4@vcu.edu
  
  
  BACKGROUND
  Supplementary Data are available at Bioinformatics online.
authors.affiliation: Department of Psychiatry, Virginia Institute for Psychiatric and Behavioral Genetics, Virginia Commonwealth University, Richmond, VA 23298, USA, Department of Psychiatry, Virginia Institute for Psychiatric and Behavioral Genetics, Virginia Commonwealth University, Richmond, VA 23298, USA.
authors.forename: Donghyung
authors.initials: D
authors.lastname: Lee
authors.affiliation: Department of Psychiatry, Virginia Institute for Psychiatric and Behavioral Genetics, Virginia Commonwealth University, Richmond, VA 23298, USA.
authors.forename: T Bernard
authors.initials: TB
authors.lastname: Bigdeli
authors.affiliation: Department of Psychiatry, Virginia Institute for Psychiatric and Behavioral Genetics, Virginia Commonwealth University, Richmond, VA 23298, USA.
authors.forename: Vernell S
authors.initials: VS
authors.lastname: Williamson
authors.affiliation: Department of Psychiatry, Virginia Institute for Psychiatric and Behavioral Genetics, Virginia Commonwealth University, Richmond, VA 23298, USA, 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, Virginia Commonwealth University, Richmond, VA 23298, USA.
authors.forename: Brien P
authors.initials: BP
authors.lastname: Riley
authors.affiliation: Department of Psychiatry, Virginia Institute for Psychiatric and Behavioral Genetics, Virginia Commonwealth University, Richmond, VA 23298, USA.
authors.forename: Ayman H
authors.initials: AH
authors.lastname: Fanous
authors.affiliation: Department of Psychiatry, Virginia Institute for Psychiatric and Behavioral Genetics, Virginia Commonwealth University, Richmond, VA 23298, USA.
authors.forename: Silviu-Alin
authors.initials: SA
authors.lastname: Bacanu
mesh_terms: D015331:Cohort Studies; D019295:Computational Biology / Q000379:methods*; D003198:Computer Simulation; D030541:Databases, Genetic; D005006:Ethnicity / Q000235:genetics*; D055106:Genome-Wide Association Study; D006801:Humans; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D012984:Software; D013223:Statistics as Topic