Genetic architecture of epigenetic and neuronal ageing rates in human brain regions

TitleGenetic architecture of epigenetic and neuronal ageing rates in human brain regions
Publication TypeJournal Article
Year of Publication2017
AuthorsLu, AT, Hannon, E, Levine, ME, Crimmins, EM, Lunnon, K, Mill, J, Geschwind, DH, Horvath, S
JournalNature Communications
Volume8
Date PublishedJun-05-2018
KeywordsGenetics
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 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 ).

URLhttp://www.nature.com/doifinder/10.1038/ncomms15353http://www.nature.com/doifinder/10.1038/ncomms15353
DOI10.1038/ncomms15353
Short TitleNat Comms
Citation Key9090
PubMed ID28516910
PubMed Central IDPMC5454371