AbstractIdentifying 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).