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PMID: 27479908 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

Tensor decomposition for multiple-tissue gene expression experiments.

Nature genetics ·Vol. 48 ·No. 9 ·2016-00-00 ·Pages 1094-100

Hore V, Viñuela A, Buil A, Knight J, McCarthy MI, Small K, Marchini J

Abstract

Genome-wide association studies of gene expression traits and other cellular phenotypes have successfully identified links between genetic variation and biological processes. The majority of discoveries have uncovered cis-expression quantitative trait locus (eQTL) effects via mass univariate testing of SNPs against gene expression in single tissues. Here we present a Bayesian method for multiple-tissue experiments focusing on uncovering gene networks linked to genetic variation. Our method decomposes the 3D array (or tensor) of gene expression measurements into a set of latent components. We identify sparse gene networks that can then be tested for association against genetic variation across the genome. We apply our method to a data set of 845 individuals from the TwinsUK cohort with gene expression measured via RNA-seq analysis in adipose, lymphoblastoid cell lines (LCLs) and skin. We uncover several gene networks with a genetic basis and clear biological and statistical significance. Extensions of this approach will allow integration of different omics, environmental and phenotypic data sets.

MeSH Terms
Adipose Tissue/metabolism Bayes Theorem Cohort Studies Gene Expression Profiling Gene Expression Regulation Gene Regulatory Networks Genetic Markers/genetics Genome-Wide Association Study Humans Lymphocytes/metabolism Phenotype Polymorphism, Single Nucleotide/genetics Quantitative Trait Loci Skin/metabolism United Kingdom
Chemicals
Genetic Markers
Authors & Affiliations
7 authors, click to expand affiliations / ORCID
Hore Victoria
Department of Statistics, University of Oxford, Oxford, UK.
Viñuela Ana
Department of Twin Research and Genetic Epidemiology, King's College London, London, UK.
Buil Alfonso
Department of Genetic Medicine and Development, University of Geneva, Geneva, Switzerland.
Knight Julian
Wellcome Trust Centre for Human Genetics, Oxford, UK.
McCarthy Mark I
Wellcome Trust Centre for Human Genetics, Oxford, UK. | Oxford Centre for Diabetes, Endocrinology and Metabolism, University of Oxford, Churchill Hospital, Oxford, UK.
Small Kerrin ORCID
Department of Twin Research and Genetic Epidemiology, King's College London, London, UK.
Marchini Jonathan ORCID
Department of Statistics, University of Oxford, Oxford, UK. | Wellcome Trust Centre for Human Genetics, Oxford, UK.
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Article Info
Journal
Nature genetics
Abbr.
Nat Genet
ISSN
1546-1718
Published
2016-00-00
Epub
2016-00-01
Pages
1094-100
Language
English
Region
United States
NLM ID
9216904
PMCID
PMC5010142
Subset
IM
Grants
European Research Council · 617306 · International
Medical Research Council · MR/L01999X/1 · United Kingdom
Wellcome Trust · United Kingdom
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