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

Ake T. Lu, Eilis Hannon, Morgan E. Levine, Eileen M. Crimmins, Katie Lunnon, Jonathan Mill, Daniel H. Geschwind, Steve Horvath*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

66 Citations (Scopus)
62 Downloads (Pure)

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).

Original languageEnglish
Article number15353
Number of pages14
JournalNature Communications
Volume8
Issue number1
Early online date18 May 2017
DOIs
Publication statusPublished - 18 May 2017

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