title: A multiple-phenotype imputation method for genetic studies.
abstract: Genetic association studies have yielded a wealth of biological discoveries. However, these studies have mostly analyzed one trait and one SNP at a time, thus failing to capture the underlying complexity of the data sets. Joint genotype-phenotype analyses of complex, high-dimensional data sets represent an important way to move beyond simple genome-wide association studies (GWAS) with great potential. The move to high-dimensional phenotypes will raise many new statistical problems. Here we address the central issue of missing phenotypes in studies with any level of relatedness between samples. We propose a multiple-phenotype mixed model and use a computationally efficient variational Bayesian algorithm to fit the model. On a variety of simulated and real data sets from a range of organisms and trait types, we show that our method outperforms existing state-of-the-art methods from the statistics and machine learning literature and can boost signals of association.
authors.affiliation: Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, UK.
authors.forename: Andrew
authors.initials: A
authors.lastname: Dahl
authors.affiliation: Human Genetics, Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, UK.|European Bioinformatics Institute (EMBL-EBI), Wellcome Trust Genome Campus, Hinxton, UK.
authors.forename: Valentina
authors.identifier: http://orcid.org/0000-0001-5057-0210
authors.initials: V
authors.lastname: Iotchkova
authors.affiliation: European Bioinformatics Institute (EMBL-EBI), Wellcome Trust Genome Campus, Hinxton, UK.
authors.forename: Amelie
authors.identifier: http://orcid.org/0000-0003-2448-0283
authors.initials: A
authors.lastname: Baud
authors.affiliation: Department of Immunology, Genetics and Pathology, Science for Life Laboratory Uppsala, Uppsala University, Uppsala, Sweden.
authors.forename: Åsa
authors.initials: Å
authors.lastname: Johansson
authors.affiliation: Department of Immunology, Genetics and Pathology, Science for Life Laboratory Uppsala, Uppsala University, Uppsala, Sweden.
authors.forename: Ulf
authors.initials: U
authors.lastname: Gyllensten
authors.affiliation: Human Genetics, Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, UK.
authors.forename: Nicole
authors.identifier: http://orcid.org/0000-0003-1095-3852
authors.initials: N
authors.lastname: Soranzo
authors.affiliation: Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, UK.
authors.forename: Richard
authors.initials: R
authors.lastname: Mott
authors.affiliation: Aviagen, Ltd., Newbridge, UK.|Roslin Institute, University of Edinburgh, Midlothian, UK.
authors.forename: Andreas
authors.initials: A
authors.lastname: Kranis
authors.affiliation: Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, UK.|Department of Statistics, University of Oxford, Oxford, UK.
authors.forename: Jonathan
authors.identifier: http://orcid.org/0000-0003-0610-8322
authors.initials: J
authors.lastname: Marchini
mesh_terms: D000465:Algorithms; D000818:Animals; D021461:Animals, Outbred Strains; D001499:Bayes Theorem; D001792:Blood Platelets / Q000502:physiology; D002645:Chickens; D005260:Female; D055106:Genome-Wide Association Study / Q000379:methods*; D006801:Humans; D008297:Male; D008957:Models, Genetic; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide; D051381:Rats; D013601:T-Lymphocytes / Q000502:physiology; D014908:Triticum / Q000235:genetics