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A multiple-phenotype imputation method for genetic studies
Univ Oxford, Wellcome Trust Ctr Human Genet, Oxford, England..
Wellcome Trust Sanger Inst, Human Genet, Wellcome Trust Genome Campus, Hinxton, England.;European Bioinformat Inst EMBL EBI, Wellcome Trust Genome Campus, Hinxton, England..
European Bioinformat Inst EMBL EBI, Wellcome Trust Genome Campus, Hinxton, England..
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology. Uppsala University, Science for Life Laboratory, SciLifeLab.
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2016 (English)In: Nature Genetics, ISSN 1061-4036, E-ISSN 1546-1718, Vol. 48, no 4, 466-472 p.Article in journal (Refereed) PublishedText
Abstract [en]

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.

Place, publisher, year, edition, pages
2016. Vol. 48, no 4, 466-472 p.
National Category
Medical Genetics
Identifiers
URN: urn:nbn:se:uu:diva-293023DOI: 10.1038/ng.3513ISI: 000372908800018PubMedID: 26901065OAI: oai:DiVA.org:uu-293023DiVA: diva2:927227
Funder
EU, European Research Council, 617306
Available from: 2016-05-11 Created: 2016-05-11 Last updated: 2016-05-11Bibliographically approved

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Johansson, ÅsaGyllensten, Ulf
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Department of Immunology, Genetics and PathologyScience for Life Laboratory, SciLifeLab
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