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Genotype × age interaction in human transcriptional ageing
journal contributionposted on 2023-05-17, 15:02 authored by Kent Jr, JW, Goring, HHH, Jac CharlesworthJac Charlesworth, Drigalenko, E, Diego, VP, Curran, JE, Johnson, MP, Dyer, TD, Cole, SA, Jowett, JBM, Mahaney, MC, Comuzzie, AG, Almasy, L, Moses, EK, Blangero, J, Williams-Blangero, S
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.
Publication titleMechanisms of Ageing and Development
Department/SchoolMenzies Institute for Medical Research
PublisherElsevier Sci Ireland Ltd
Place of publicationCustomer Relations Manager, Bay 15, Shannon Industrial Estate Co, Clare, Ireland
Rights statementCopyright 2012 Elsevier Ireland Ltd.