A meta-analysis of genome-wide association studies of epigenetic age acceleration.
Journal
PLoS genetics
ISSN: 1553-7404
Titre abrégé: PLoS Genet
Pays: United States
ID NLM: 101239074
Informations de publication
Date de publication:
11 2019
11 2019
Historique:
received:
19
03
2019
accepted:
16
08
2019
revised:
02
12
2019
pubmed:
19
11
2019
medline:
19
2
2020
entrez:
19
11
2019
Statut:
epublish
Résumé
'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.
Identifiants
pubmed: 31738745
doi: 10.1371/journal.pgen.1008104
pii: PGENETICS-D-19-00433
pmc: PMC6886870
doi:
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
e1008104Subventions
Organisme : NIA NIH HHS
ID : U01 AG060908
Pays : United States
Organisme : Wellcome Trust
ID : 104036/Z/14/Z
Pays : United Kingdom
Organisme : Chief Scientist Office
ID : CZD/16/6
Pays : United Kingdom
Organisme : Medical Research Council
ID : G0700704
Pays : United Kingdom
Organisme : Medical Research Council
ID : MC_UU_00007/10
Pays : United Kingdom
Organisme : Medical Research Council
ID : MR/K026992/1
Pays : United Kingdom
Déclaration de conflit d'intérêts
The authors have declared that no competing interests exist.
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