Genetic variants near MLST8 and DHX57 affect the epigenetic age of the cerebellum.

2.50
Hdl Handle:
http://hdl.handle.net/11287/620268
Title:
Genetic variants near MLST8 and DHX57 affect the epigenetic age of the cerebellum.
Authors:
Lu, A. T.; Hannon, E.; Levine, M. E.; Hao, K.; Crimmins, E. M.; Lunnon, K.; Kozlenkov, A.; Mill, Jonathan; Dracheva, S.; Horvath, S.
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.
Citation:
Genetic variants near MLST8 and DHX57 affect the epigenetic age of the cerebellum. 2016, 7:10561 Nat Commun
Publisher:
Nature
Journal:
Nature communications
Issue Date:
2-Feb-2016
URI:
http://hdl.handle.net/11287/620268
DOI:
10.1038/ncomms10561
PubMed ID:
26830004
Additional Links:
http://dx.doi.org/10.1038/ncomms10561
Note:
This article is freely available 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; 2016 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.authorHao, K.en
dc.contributor.authorCrimmins, E. M.en
dc.contributor.authorLunnon, K.en
dc.contributor.authorKozlenkov, A.en
dc.contributor.authorMill, Jonathanen
dc.contributor.authorDracheva, S.en
dc.contributor.authorHorvath, S.en
dc.date.accessioned2017-03-13T09:52:02Z-
dc.date.available2017-03-13T09:52:02Z-
dc.date.issued2016-02-02-
dc.identifier.citationGenetic variants near MLST8 and DHX57 affect the epigenetic age of the cerebellum. 2016, 7:10561 Nat Communen
dc.identifier.issn2041-1723-
dc.identifier.pmid26830004-
dc.identifier.doi10.1038/ncomms10561-
dc.identifier.urihttp://hdl.handle.net/11287/620268-
dc.description.abstractDNA 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
dc.language.isoenen
dc.publisherNatureen
dc.relation.urlhttp://dx.doi.org/10.1038/ncomms10561en
dc.rightsArchived with thanks to Nature communicationsen
dc.subjectWessex Classification Subject Headings::Oncology. Pathology.::Geneticsen
dc.titleGenetic variants near MLST8 and DHX57 affect the epigenetic age of the cerebellum.en
dc.typeJournal Articleen
dc.identifier.journalNature communicationsen
dc.description.noteThis article is freely available 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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