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Genotype age interaction in human transcriptional ageing

Citation

Kent Jr, JW and Goring, HHH and Charlesworth, JC and Drigalenko, E and Diego, VP and Curran, JE and Johnson, MP and Dyer, TD and Cole, SA and Jowett, JBM and Mahaney, MC and Comuzzie, AG and Almasy, L and Moses, EK and Blangero, J and Williams-Blangero, S, Genotype age interaction in human transcriptional ageing, Mechanisms of Ageing and Development, 133, (9-10) pp. 581-590. ISSN 0047-6374 (2012) [Refereed Article]

Copyright Statement

Copyright 2012 Elsevier Ireland Ltd.

DOI: doi:10.1016/j.mad.2012.07.005

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.

Item Details

Item Type:Refereed Article
Keywords:transcriptional ageing, genotype by age interaction, ubiquitins, UBQLNL, cancer risk gene
Research Division:Medical and Health Sciences
Research Group:Clinical Sciences
Research Field:Medical Genetics (excl. Cancer Genetics)
Objective Division:Health
Objective Group:Specific Population Health (excl. Indigenous Health)
Objective Field:Health Related to Ageing
Author:Charlesworth, JC (Dr Jac Charlesworth)
ID Code:81554
Year Published:2012
Web of Science® Times Cited:11
Deposited By:Menzies Institute for Medical Research
Deposited On:2012-12-13
Last Modified:2017-11-02
Downloads:0

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