PT  - JOURNAL ARTICLE
AU  - Trevor Martin
AU  - Hunter B. Fraser
TI  - Genetic control of age-related gene expression and complex traits in the human brain
AID  - 10.1101/125195
DP  - 2017 Jan 01
TA  - bioRxiv
PG  - 125195
4099  - http://biorxiv.org/content/early/2017/04/07/125195.short
4100  - http://biorxiv.org/content/early/2017/04/07/125195.full
AB  - Age is the primary risk factor for many of the most common human diseases—particularly neurodegenerative diseases—yet we currently have a very limited understanding of how each individual’s genome affects the aging process. Here we introduce a method to map genetic variants associated with age-related gene expression patterns, which we call temporal expression quantitative trait loci (teQTL). We found that these loci are markedly enriched in the human brain and are associated with neurodegenerative diseases such as Alzheimer’s disease and Creutzfeldt-Jakob disease. Examining potential molecular mechanisms, we found that age-related changes in DNA methylation can explain some cis-acting teQTLs, and that trans-acting teQTLs can be mediated by microRNAs. Our results suggest that genetic variants modifying age-related patterns of gene expression, acting through both cis- and trans-acting molecular mechanisms, could play a role in the pathogenesis of diverse neurological diseases.