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

Andrew Anand Brown, Zhihao Ding, Ana Viñuela, Dan Glass, Leopold Parts, Tim Spector, John Winn, Richard Durbin (Lead / Corresponding author)

Research output: Contribution to journalArticlepeer-review

6 Citations (Scopus)
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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 (P<5:38×10-5). These phenotypes are more heritable (h2 = 0:32) 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 analysis methods combined with biological knowledge can produce more reliable phenotypes with less stochastic noise than the individual gene expression levels, which increases our power to discover biologically relevant associations. These phenotypes could also be applied to discover associations with other environmental factors.

Original languageEnglish
Pages (from-to)839-847
Number of pages9
JournalG3: Genes, Genomes, Genetics
Volume5
Issue number5
DOIs
Publication statusPublished - 1 May 2015

Keywords

  • Aging
  • Factor analysis
  • Gene expression
  • Heritability
  • Linear mixed models

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