Pathway-based factor analysis of gene expression data produces highly heritable phenotypes that associate with age

G3 : Genes - Genomes - Genetics
Andrew Anand BrownRichard Durbin

Abstract

Statistical factor analysis methods have previously been used to remove noise components from high-dimensional data prior to genetic association mapping and, in a guided fashion, to summarize biologically relevant sources of variation. Here, we show how the derived factors summarizing pathway expression can be used to analyze the relationships between expression, heritability, and aging. We used skin gene expression data from 647 twins from the MuTHER Consortium and applied factor analysis to concisely summarize patterns of gene expression to remove broad confounding influences and to produce concise pathway-level phenotypes. We derived 930 "pathway phenotypes" that summarized patterns of variation across 186 KEGG pathways (five phenotypes per pathway). We identified 69 significant associations of age with phenotype from 57 distinct KEGG pathways at a stringent Bonferroni threshold ([Formula: see text]). These phenotypes are more heritable ([Formula: see text]) than gene expression levels. On average, expression levels of 16% of genes within these pathways are associated with age. Several significant pathways relate to metabolizing sugars and fatty acids; others relate to insulin signaling. We have demonstrated that factor anal...Continue Reading

References

Dec 17, 2002·Nature·Martin HolzenbergerYves Le Bouc
Oct 14, 2003·Biochemical Pharmacology·Alfonso PompellaAlessandro F Casini
Dec 19, 2003·Nucleic Acids Research·Minoru KanehisaMasahiro Hattori
Jun 11, 2004·Nature·Tao LuBruce A Yankner
Aug 19, 2007·Nature·Toren FinkelMaria A Blasco
Oct 3, 2007·PLoS Genetics·Jeffrey T Leek, John D Storey
Sep 4, 2008·Proceedings of the National Academy of Sciences of the United States of America·Bradley J WillcoxJ David Curb
Jan 10, 2009·Nature Protocols·Da Wei HuangRichard A Lempicki
Feb 5, 2009·Bioinformatics·João Pedro de MagalhãesGeorge M Church
Mar 12, 2010·Nature·Joseph K PickrellJonathan K Pritchard
Feb 2, 2011·PLoS Genetics·Leopold PartsRichard Durbin
Feb 10, 2011·PLoS Genetics·Alexandra C NicaUNKNOWN MuTHER Consortium
Jan 19, 2012·International Journal of Epidemiology·Alireza MoayyeriTimothy D Spector
Feb 23, 2012·Scientific Reports·Riekelt H HoutkooperJohan Auwerx
May 24, 2012·Diabetes·Nir BarzilaiAndrzej Bartke
Jun 7, 2012·G3 : Genes - Genomes - Genetics·Ana ViñuelaJan E Kammenga
Sep 4, 2012·Nature Genetics·Elin GrundbergUNKNOWN Multiple Tissue Human Expression Resource (MuTHER) Consortium
Apr 25, 2013·Nature Reviews. Cancer·João Pedro de Magalhães
Jul 31, 2013·Genome Biology·Daniel GlassTim D Spector

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Citations

Aug 19, 2016·Frontiers in Aging Neuroscience·Candice L Brinkmeyer-LangfordJames J Cai
Dec 12, 2017·Human Molecular Genetics·Ana ViñuelaKerrin S Small
Dec 30, 2017·American Journal of Transplantation : Official Journal of the American Society of Transplantation and the American Society of Transplant Surgeons·R N SmithR B Colvin
Dec 31, 2017·American Journal of Transplantation : Official Journal of the American Society of Transplantation and the American Society of Transplant Surgeons·R N SmithR B Colvin

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Methods Mentioned

BETA
RNA-seq
biopsy

Software Mentioned

DAVID
PEER
Illumina Beadstudio
Ensembl
lme4

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