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    Genotype × age interaction in human transcriptional ageing

    Access Status
    Fulltext not available
    Authors
    Kent, J.
    Göring, H.
    Charlesworth, J.
    Drigalenko, E.
    Diego, V.
    Curran, J.
    Johnson, M.
    Dyer, T.
    Cole, S.
    Jowett, J.
    Mahaney, M.
    Comuzzie, A.
    Almasy, L.
    Moses, Eric
    Blangero, J.
    Williams-Blangero, S.
    Date
    2012
    Type
    Journal Article
    
    Metadata
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    Citation
    Kent, J. and Göring, H. and Charlesworth, J. and Drigalenko, E. and Diego, V. and Curran, J. and Johnson, M. et al. 2012. Genotype × age interaction in human transcriptional ageing. Mechanisms of Ageing and Development. 133 (9-10): pp. 581-590.
    Source Title
    Mechanisms of Ageing and Development
    DOI
    10.1016/j.mad.2012.07.005
    ISSN
    0047-6374
    School
    School of Biomedical Sciences
    URI
    http://hdl.handle.net/20.500.11937/2992
    Collection
    • Curtin Research Publications
    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.

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