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Depositordc.contributorClarke, Toni
Funderdc.contributor.otherWellcome Trusten_UK
Data Creatordc.creatorClarke, Toni
Data Creatordc.creatorMcIntosh, Andrew M
Data Creatordc.creatorMarioni, Riccardo
Data Creatordc.creatorGibson, Jude
Date Accessioneddc.date.accessioned2019-10-15T15:04:28Z
Date Availabledc.date.available2019-11-19
Citationdc.identifier.citationGibson, Jude; Clarke, Toni; McIntosh, Andrew M; Marioni, Riccardo. (2019). GWAS summary stats for meta-analysis of epigenetic age acceleration - Gibson et al, (2019), [dataset]. University of Edinburgh. Centre for Clinical Brain Sciences. https://doi.org/10.7488/ds/2631en
Persistent Identifierdc.identifier.urihttp://hdl.handle.net/10283/3427
Persistent Identifierdc.identifier.urihttps://doi.org/10.7488/ds/2631
Dataset Description (abstract)dc.description.abstract'Epigenetic age acceleration' is a valuable biomarker of ageing, predictive of morbidity and mortality, but for which the underlying biological mechanisms are not well established. Two commonly used measures, derived from DNA methylation, are Horvath-based (Horvath-EAA) and Hannum-based (Hannum-EAA) epigenetic age acceleration. We conducted genome-wide association studies of Horvath-EAA and Hannum-EAA in 13,493 unrelated individuals of European ancestry, to elucidate genetic determinants of differential epigenetic ageing. We identified ten independent SNPs associated with Horvath-EAA, five of which are novel. We also report 21 Horvath-EAA-associated genes including several involved in metabolism (NHLRC, TPMT) and immune system pathways (TRIM59, EDARADD). GWAS of Hannum-EAA identified one associated variant (rs1005277), and implicated 12 genes including several involved in innate immune system pathways (UBE2D3, MANBA, TRIM46), with metabolic functions (UBE2D3, MANBA), or linked to lifespan regulation (CISD2). Both measures had nominal inverse genetic correlations with father’s age at death, a rough proxy for lifespan. Nominally significant genetic correlations between Hannum-EAA and lifestyle factors including smoking behaviours and education support the hypothesis that Hannum-based epigenetic ageing is sensitive to variations in environment, whereas Horvath-EAA is a more stable cellular ageing process. We identified novel SNPs and genes associated with epigenetic age acceleration, and highlighted differences in the genetic architecture of Horvath-based and Hannum-based epigenetic ageing measures. Understanding the biological mechanisms underlying individual differences in the rate of epigenetic ageing could help explain different trajectories of age-related decline.en_UK
Languagedc.language.isoengen_UK
Publisherdc.publisherUniversity of Edinburgh. Centre for Clinical Brain Sciencesen_UK
Relation (Is Referenced By)dc.relation.isreferencedbyhttps://doi.org/10.1371/journal.pgen.1008104
Rightsdc.rightsCreative Commons Attribution 4.0 International Public Licenseen
Subjectdc.subjectGWASen_UK
Subjectdc.subjectepigenetic ageen_UK
Subjectdc.subjectmethylationen_UK
Subject Classificationdc.subject.classificationBiological Sciences::Human Geneticsen_UK
Titledc.titleGWAS summary stats for meta-analysis of epigenetic age acceleration - Gibson et al, (2019)en_UK
Typedc.typedataseten_UK

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