PT  - JOURNAL ARTICLE
AU  - Ana Viñuela
AU  - Andrew A Brown
AU  - Alfonso Buil
AU  - Pei-Chien Tsai
AU  - Matthew N Davies
AU  - Jordana T Bell
AU  - Emmanouil T Dermitzakis
AU  - Timothy D Spector
AU  - Kerrin S Small
TI  - Age-dependent changes in mean and variance of gene expression across tissues in a twin cohort
AID  - 10.1101/063883
DP  - 2016 Jan 01
TA  - bioRxiv
PG  - 063883
4099  - http://biorxiv.org/content/early/2016/07/14/063883.short
4100  - http://biorxiv.org/content/early/2016/07/14/063883.full
AB  - Gene expression changes with age have consequences for healthy aging and disease development. Here we investigate age-related changes in gene expression measured by RNA-seq of fat, skin, whole blood and derived lymphoblastoid cell lines (LCLs) expression from ~800 adult female twins. We see evidence of up to 60% shared transcriptional age-related effects across tissues on level of expression and 47% on splicing; amongst these we highlight effects on genes involved in diseases such as Alzheimer and cancer. We identify 137 genes with age-related changes in variance and 42 genes with age-related discordance between genetically identical individuals; implying the latter are driven by environmental effects. Investigation of methylation effects observed a widespread and stronger effect of age on methylation than expression however we did not find a strong relationship between changes in both expression and methylation. In contrast, we find 4 significant examples where the ageing process is modulated by genetic variants. In summary, we demonstrate that aging affects the splicing, level and variance of expression, and that these processes can be both environmentally and genetically influenced.