Title | Genetic architecture of epigenetic and neuronal ageing rates in human brain regions |
Publication Type | Journal Article |
Year of Publication | 2017 |
Authors | Lu, AT, Hannon, E, Levine, ME, Crimmins, EM, Lunnon, K, Mill, J, Geschwind, DH, Horvath, S |
Journal | Nature Communications |
Volume | 8 |
Date Published | Jun-05-2018 |
Keywords | Genetics |
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 ). |
URL | http://www.nature.com/doifinder/10.1038/ncomms15353http://www.nature.com/doifinder/10.1038/ncomms15353 |
DOI | 10.1038/ncomms15353 |
Short Title | Nat Comms |
Citation Key | 9090 |
PubMed ID | 28516910 |
PubMed Central ID | PMC5454371 |
Grant List | U01 AG009740 / AG / NIA NIH HHS / United States R01 AG036042 / AG / NIA NIH HHS / United States P30 AG010161 / AG / NIA NIH HHS / United States U34 AG051425 / AG / NIA NIH HHS / United States R01 AG042511 / AG / NIA NIH HHS / United States R01 AG015819 / AG / NIA NIH HHS / United States |