Genetic architecture of epigenetic and neuronal ageing rates in human brain regions
Lu, AT; Hannon, E; Levine, ME; et al.Crimmins, EM; Lunnon, K; Mill, J; Geschwind, DH; Horvath, S
Date: 18 May 2017
Journal
Nature Communications
Publisher
Springer Nature
Publisher DOI
Related links
Abstract
Identifying genes regulating the pace of epigenetic ageing represents a new frontier in genome-wide association studies (GWASs). Here using 1,796 brain samples from 1,163 individuals, we carry out a GWAS of two DNA methylation-based biomarkers of brain age: the epigenetic ageing rate and estimated proportion of neurons. Locus 17q11.2 ...
Identifying genes regulating the pace of epigenetic ageing represents a new frontier in genome-wide association studies (GWASs). Here using 1,796 brain samples from 1,163 individuals, we carry out a GWAS of two DNA methylation-based biomarkers of brain age: the epigenetic ageing rate and estimated proportion of neurons. Locus 17q11.2 is significantly associated (P=4.5 × 10(-9)) with the ageing rate across five brain regions and harbours a cis-expression quantitative trait locus for EFCAB5 (P=3.4 × 10(-20)). Locus 1p36.12 is significantly associated (P=2.2 × 10(-8)) with epigenetic ageing of the prefrontal cortex, independent of the proportion of neurons. Our GWAS of the proportion of neurons identified two genome-wide significant loci (10q26 and 12p13.31) and resulted in a gene set that overlaps significantly with sets found by GWAS of age-related macular degeneration (P=1.4 × 10(-12)), ulcerative colitis (P<1.0 × 10(-20)), type 2 diabetes (P=2.8 × 10(-13)), hip/waist circumference in men (P=1.1 × 10(-9)), schizophrenia (P=1.6 × 10(-9)), cognitive decline (P=5.3 × 10(-4)) and Parkinson's disease (P=8.6 × 10(-3)).
Institute of Biomedical & Clinical Science
Collections of Former Colleges
Item views 0
Full item downloads 0