A multiple-phenotype imputation method for genetic studies

Dahl, AndrewUniv Oxford, Wellcome Trust Ctr Human Genet, Oxford, England. (author)

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.

Iotchkova, ValentinaWellcome Trust Sanger Inst, Human Genet, Wellcome Trust Genome Campus, Hinxton, England.;European Bioinformat Inst EMBL EBI, Wellcome Trust Genome Campus, Hinxton, England. (author)
Baud, AmelieEuropean Bioinformat Inst EMBL EBI, Wellcome Trust Genome Campus, Hinxton, England. (author)
Johansson, ÅsaUppsala universitet,Institutionen för immunologi, genetik och patologi,Science for Life Laboratory, SciLifeLab(Swepub:uu)asjoh108 (author)
Gyllensten, UlfUppsala universitet,Institutionen för immunologi, genetik och patologi,Science for Life Laboratory, SciLifeLab(Swepub:uu)ulfgyll (author)
Soranzo, NicoleWellcome Trust Sanger Inst, Human Genet, Wellcome Trust Genome Campus, Hinxton, England. (author)
Mott, RichardUniv Oxford, Wellcome Trust Ctr Human Genet, Oxford, England. (author)
Kranis, AndreasAviagen Ltd, Newbridge, England.;Univ Edinburgh, Roslin Inst, Edinburgh EH8 9YL, Midlothian, Scotland. (author)
Marchini, JonathanUniv Oxford, Wellcome Trust Ctr Human Genet, Oxford, England.;Univ Oxford, Dept Stat, Oxford OX1 3TG, England. (author)
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. (creator_code:org_t)

In:Nature Genetics: Springer Science and Business Media LLC48:4, s. 466-4721061-40361546-1718

By the author/editor: Dahl, Andrew; Iotchkova, Valen ...; Baud, Amelie; Johansson, Åsa; Gyllensten, Ulf; Soranzo, Nicole; show more...; Mott, Richard; Kranis, Andreas; Marchini, Jonath ...; show less...

About the subject

MEDICAL AND HEALTH SCIENCES: MEDICAL AND HEAL ...; and Basic Medicine; and Medical Genetics

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