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Genotype × age interaction in human transcriptional ageing
journal contribution
posted 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, SIndividual 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.
History
Publication title
Mechanisms of Ageing and DevelopmentVolume
133Issue
9-10Pagination
581-590ISSN
0047-6374Department/School
Menzies Institute for Medical ResearchPublisher
Elsevier Sci Ireland LtdPlace of publication
Customer Relations Manager, Bay 15, Shannon Industrial Estate Co, Clare, IrelandRights statement
Copyright 2012 Elsevier Ireland Ltd.Repository Status
- Restricted