title: Genotype×age interaction in human transcriptional ageing.
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.
authors.affiliation: Department of Genetics, Texas Biomedical Research Institute, San Antonio, TX 78245, USA. jkent@txbiomedgenetics.org
authors.forename: Jack W
authors.initials: JW
authors.lastname: Kent
authors.forename: Harald H H
authors.initials: HH
authors.lastname: Göring
authors.forename: Jac C
authors.initials: JC
authors.lastname: Charlesworth
authors.forename: Eugene
authors.initials: E
authors.lastname: Drigalenko
authors.forename: Vincent P
authors.initials: VP
authors.lastname: Diego
authors.forename: Joanne E
authors.initials: JE
authors.lastname: Curran
authors.forename: Matthew P
authors.initials: MP
authors.lastname: Johnson
authors.forename: Thomas D
authors.initials: TD
authors.lastname: Dyer
authors.forename: Shelley A
authors.initials: SA
authors.lastname: Cole
authors.forename: Jeremy B M
authors.initials: JB
authors.lastname: Jowett
authors.forename: Michael C
authors.initials: MC
authors.lastname: Mahaney
authors.forename: Anthony G
authors.initials: AG
authors.lastname: Comuzzie
authors.forename: Laura
authors.initials: L
authors.lastname: Almasy
authors.forename: Eric K
authors.initials: EK
authors.lastname: Moses
authors.forename: John
authors.initials: J
authors.lastname: Blangero
authors.forename: Sarah
authors.initials: S
authors.lastname: Williams-Blangero
mesh_terms: D000328:Adult; D000367:Age Factors; D000368:Aged; D000375:Aging / Q000502:physiology*; D002648:Child; D002675:Child, Preschool; D005260:Female; D005500:Follow-Up Studies; D005786:Gene Expression Regulation / Q000502:physiology*; D055106:Genome-Wide Association Study; D005838:Genotype; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008297:Male; D017058:Mexican Americans; D008875:Middle Aged; D009369:Neoplasms / Q000453:epidemiology / Q000235:genetics / Q000378:metabolism; D012307:Risk Factors; D013781:Texas / Q000453:epidemiology; D014158:Transcription, Genetic / Q000502:physiology*