dc.contributor.author | Lu, AT | |
dc.contributor.author | Hannon, E | |
dc.contributor.author | Levine, ME | |
dc.contributor.author | Hao, K | |
dc.contributor.author | Crimmins, EM | |
dc.contributor.author | Lunnon, Katie | |
dc.contributor.author | Kozlenkov, A | |
dc.contributor.author | Mill, J | |
dc.contributor.author | Dracheva, S | |
dc.contributor.author | Horvath, S | |
dc.date.accessioned | 2016-02-12T08:49:57Z | |
dc.date.issued | 2016-02-02 | |
dc.description.abstract | DNA methylation (DNAm) levels lend themselves for defining an epigenetic biomarker of aging known as the 'epigenetic clock'. Our genome-wide association study (GWAS) of cerebellar epigenetic age acceleration identifies five significant (P<5.0 × 10(-8)) SNPs in two loci: 2p22.1 (inside gene DHX57) and 16p13.3 near gene MLST8 (a subunit of mTOR complex 1 and 2). We find that the SNP in 16p13.3 has a cis-acting effect on the expression levels of MLST8 (P=6.9 × 10(-18)) in most brain regions. In cerebellar samples, the SNP in 2p22.1 has a cis-effect on DHX57 (P=4.4 × 10(-5)). Gene sets found by our GWAS analysis of cerebellar age acceleration exhibit significant overlap with those of Alzheimer's disease (P=4.4 × 10(-15)), age-related macular degeneration (P=6.4 × 10(-6)), and Parkinson's disease (P=2.6 × 10(-4)). Overall, our results demonstrate the utility of a new paradigm for understanding aging and age-related diseases: it will be fruitful to use epigenetic tissue age as endophenotype in GWAS. | en_GB |
dc.description.sponsorship | National Institutes of Health | en_GB |
dc.identifier.citation | Vol. 7, pp. 10561 - | en_GB |
dc.identifier.doi | 10.1038/ncomms10561 | |
dc.identifier.grantnumber | NIA/NIH 5R01AG042511-02 | en_GB |
dc.identifier.other | ncomms10561 | |
dc.identifier.uri | http://hdl.handle.net/10871/19746 | |
dc.language.iso | en | en_GB |
dc.publisher | Nature Publishing Group | en_GB |
dc.relation.url | http://www.ncbi.nlm.nih.gov/pubmed/26830004 | en_GB |
dc.relation.url | http://www.nature.com/ncomms/2016/160202/ncomms10561/full/ncomms10561.html | en_GB |
dc.rights | Copyright © 2016 Macmillan Publishers Limited. All Rights Reserved. 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.subject | Fluids and plasma physics | en_GB |
dc.subject | Biological sciences | en_GB |
dc.subject | Neuroscience | en_GB |
dc.title | Genetic variants near MLST8 and DHX57 affect the epigenetic age of the cerebellum. | en_GB |
dc.type | Article | en_GB |
dc.date.available | 2016-02-12T08:49:57Z | |
exeter.place-of-publication | England | |
dc.description | Published online | en_GB |
dc.description | Journal Article | en_GB |
dc.identifier.eissn | 2041-1723 | |
dc.identifier.journal | Nature Communications | en_GB |