Genotype × age interaction in human transcriptional ageing
|dc.identifier.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.|
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.
|dc.title||Genotype × age interaction in human transcriptional ageing|
|dcterms.source.title||Mechanisms of Ageing and Development|
|curtin.department||School of Biomedical Sciences|
|curtin.accessStatus||Fulltext not available|
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