Genotype × age interaction in human transcriptional ageing

Jack W. Kent, Harald H.H. Göring, Jac C. Charlesworth, Eugene Drigalenko, Vincent P. Diego, Joanne E. Curran, Matthew P. Johnson, Thomas D. Dyer, Shelley A. Cole, Jeremy B.M. Jowett, Michael C. Mahaney, Anthony G. Comuzzie, Laura Almasy, Eric K. Moses, John Blangero, Sarah Williams-Blangero

    Research output: Contribution to journalArticlepeer-review

    23 Scopus citations

    Abstract

    Individual differences in biological ageing (i.e., the rate of physiological response to the passage of time) may be due in part to genotype-specific variation in gene action. However, the sources of heritable variation in human age-related gene expression profiles are largely unknown. We have profiled genome-wide expression in peripheral blood mononuclear cells from 1240 individuals in large families and found 4472 human autosomal transcripts, representing ∼4349 genes, significantly correlated with age. We identified 623 transcripts that show genotype by age interaction in addition to a main effect of age, defining a large set of novel candidates for characterization of the mechanisms of differential biological ageing. We applied a novel SNP genotype. ×. age interaction test to one of these candidates, the ubiquilin-like gene UBQLNL, and found evidence of joint cis-association and genotype by age interaction as well as trans-genotype by age interaction for UBQLNL expression. Both UBQLNL expression levels at recruitment and cis genotype are associated with longitudinal cancer risk in our study cohort.

    Original languageEnglish (US)
    Pages (from-to)581-590
    Number of pages10
    JournalMechanisms of Ageing and Development
    Volume133
    Issue number9-10
    DOIs
    StatePublished - Sep 2012

    Keywords

    • Cancer risk gene
    • Genotype by age interaction
    • Transcriptional ageing
    • UBQLNL
    • Ubiquitins

    ASJC Scopus subject areas

    • Aging
    • Developmental Biology

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