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Mech Ageing Dev. 2012 Sep-Oct;133(9-10):581-90. doi: 10.1016/j.mad.2012.07.005. Epub 2012 Jul 31.

Genotype×age interaction in human transcriptional ageing.

Author information

  • 1Department of Genetics, Texas Biomedical Research Institute, San Antonio, TX 78245, USA. jkent@txbiomedgenetics.org

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.

Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

PMID:
22871458
[PubMed - indexed for MEDLINE]
PMCID:
PMC3541784
Free PMC Article

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