| dc.contributor.author | Lu, AT | |
| dc.contributor.author | Hannon, E | |
| dc.contributor.author | Levine, ME | |
| dc.contributor.author | Crimmins, EM | |
| dc.contributor.author | Lunnon, K | |
| dc.contributor.author | Mill, J | |
| dc.contributor.author | Geschwind, DH | |
| dc.contributor.author | Horvath, S | |
| dc.date.accessioned | 2017-06-02T14:44:53Z | |
| dc.date.issued | 2017-05-18 | |
| dc.description.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)). | en_GB |
| dc.description.sponsorship | The study was supported by the Paul G. Allen Family Foundation and by the National Institutes of Health (NIA/NIH 5R01AG042511-02). The Religious Order Study (GWAS data sets 6 and 7) was supported by National Institutes of Health (NIAGADS P30AG10161, R01AG15819, AG/NIA NIH R01AG17917 and AG/NIA NIH HHS R01AG36042). | en_GB |
| dc.identifier.citation | Vol. 8, article 15353 | en_GB |
| dc.identifier.doi | 10.1038/ncomms15353 | |
| dc.identifier.uri | http://hdl.handle.net/10871/27780 | |
| dc.language.iso | en | en_GB |
| dc.publisher | Springer Nature | en_GB |
| dc.relation.url | https://www.ncbi.nlm.nih.gov/pubmed/28516910 | en_GB |
| dc.rights | This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ | en_GB |
| dc.title | Genetic architecture of epigenetic and neuronal ageing rates in human brain regions | en_GB |
| dc.type | Article | en_GB |
| dc.date.available | 2017-06-02T14:44:53Z | |
| exeter.place-of-publication | England | en_GB |
| dc.description | This is the final version of the article. Available from Springer Nature via the DOI in this record. | en_GB |
| dc.identifier.journal | Nature Communications | en_GB |
| dc.source.uri | http://creativecommons.org/licenses/by/4.0/ | |
