Genetic architecture of epigenetic and neuronal ageing rates in human brain regions.

2.50
Hdl Handle:
http://hdl.handle.net/11287/620424
Title:
Genetic architecture of epigenetic and neuronal ageing rates in human brain regions.
Authors:
Lu, A. T.; Hannon, E.; Levine, M. E.; Crimmins, E. M.; Lunnon, K.; Mill, Jonathan; Geschwind, D. H.; Horvath, S.
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)).
Citation:
Genetic architecture of epigenetic and neuronal ageing rates in human brain regions. 2017, 8:15353 Nat Commun
Publisher:
Nature
Journal:
Nature Communications
Issue Date:
18-May-2017
URI:
http://hdl.handle.net/11287/620424
DOI:
10.1038/ncomms15353
PubMed ID:
28516910
Additional Links:
https://www.ncbi.nlm.nih.gov/pmc/articles/pmid/28516910/
Note:
This article is freely available online via Open Access. Click on the Additional Link above to access the full-text via the publisher's site.
Type:
Journal Article
Language:
en
ISSN:
2041-1723
Appears in Collections:
Honorary contracts publications; 2017 RD&E publications

Full metadata record

DC FieldValue Language
dc.contributor.authorLu, A. T.en
dc.contributor.authorHannon, E.en
dc.contributor.authorLevine, M. E.en
dc.contributor.authorCrimmins, E. M.en
dc.contributor.authorLunnon, K.en
dc.contributor.authorMill, Jonathanen
dc.contributor.authorGeschwind, D. H.en
dc.contributor.authorHorvath, S.en
dc.date.accessioned2017-10-04T13:46:32Z-
dc.date.available2017-10-04T13:46:32Z-
dc.date.issued2017-05-18-
dc.identifier.citationGenetic architecture of epigenetic and neuronal ageing rates in human brain regions. 2017, 8:15353 Nat Communen
dc.identifier.issn2041-1723-
dc.identifier.pmid28516910-
dc.identifier.doi10.1038/ncomms15353-
dc.identifier.urihttp://hdl.handle.net/11287/620424-
dc.description.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)).en
dc.language.isoenen
dc.publisherNatureen
dc.relation.urlhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/28516910/en
dc.rightsArchived with thanks to Nature communicationsen
dc.subjectWessex Classification Subject Headings::Oncology. Pathology.::Geneticsen
dc.titleGenetic architecture of epigenetic and neuronal ageing rates in human brain regions.en
dc.typeJournal Articleen
dc.identifier.journalNature Communicationsen
dc.description.noteThis article is freely available online via Open Access. Click on the Additional Link above to access the full-text via the publisher's site.en
dc.type.versionPublisheden

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