Genotype×age interaction in human transcriptional ageing
| Autor: | Matthew P. Johnson, Eric K. Moses, Shelley A. Cole, Jeremy B M Jowett, Harald H H Göring, Joanne E. Curran, Vincent P. Diego, John Blangero, Jack W. Kent, Jac Charlesworth, Thomas D. Dyer, Anthony G. Comuzzie, Michael C. Mahaney, Eugene Drigalenko, Laura Almasy, Sarah Williams-Blangero |
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| Rok vydání: | 2012 |
| Předmět: |
Adult
Male Aging Genotype Transcription Genetic Biology Peripheral blood mononuclear cell Article Risk Factors Neoplasms Mexican Americans Gene expression Humans SNP Child Gene Aged Genetics Age Factors Infant Newborn Infant Middle Aged Texas Gene Expression Regulation Ageing Child Preschool Cohort Female Cancer risk Follow-Up Studies Genome-Wide Association Study Developmental Biology |
| Zdroj: | Mechanisms of Ageing and Development. 133:581-590 |
| ISSN: | 0047-6374 |
| DOI: | 10.1016/j.mad.2012.07.005 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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