Genetic architecture of epigenetic and neuronal ageing rates in human brain regions.
basic_science · Level V
Where this comes from
- Record sourced from PubMed, PMID 28516910.
- Also identified by DOI 10.1038/ncomms15353 and PMC identifier 5454371.
- Licence recorded as CC BY.
- The licence permits redistribution, so the abstract is shown in full and the full text is available from the publisher.
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<sup>-9</sup>) with the ageing rate across five brain regions and harbours a cis-expression quantitative trait locus for EFCAB5 (P=3.4 × 10<sup>-20</sup>). Locus 1p36.12 is significantly associated (P=2.2 × 10<sup>-8</sup>) 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<sup>-12</sup>), ulcerative colitis (P<1.0 × 10<sup>-20</sup>), type 2 diabetes (P=2.8 × 10<sup>-13</sup>), hip/waist circumference in men (P=1.1 × 10<sup>-9</sup>), schizophrenia (P=1.6 × 10<sup>-9</sup>), cognitive decline (P=5.3 × 10<sup>-4</sup>) and Parkinson's disease (P=8.6 × 10<sup>-3</sup>).
Medical subject headings
- Aging
- Cognitive Dysfunction
- Epigenesis, Genetic
- Genome, Human
- Nerve Tissue Proteins
- Neurodegenerative Diseases