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A meta-analysis of genome-wide association studies of epigenetic age acceleration

Gibson, Jude ; Russ, Tom C ; Clarke, Toni-Kim ; Howard, David M ; Hillary, Robert F ; Evans, Kathryn L ; Walker, Rosie M ; Bermingham, Mairead L ; Morris, Stewart W ; Campbell, Archie ; Hayward, Caroline ; Murray, Alison D ; Porteous, David J ; Horvath, Steve ; Lu, Ake T ; McIntosh, Andrew M ; Whalley, Heather C ; Marioni, Riccardo E Greally, John M.

PLoS genetics, 2019-11, Vol.15 (11), p.e1008104-e1008104 [Periódico revisado por pares]

United States: Public Library of Science

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A meta-analysis of genome-wide association studies of epigenetic age acceleration
Autor: Gibson, Jude ; Russ, Tom C ; Clarke, Toni-Kim ; Howard, David M ; Hillary, Robert F ; Evans, Kathryn L ; Walker, Rosie M ; Bermingham, Mairead L ; Morris, Stewart W ; Campbell, Archie ; Hayward, Caroline ; Murray, Alison D ; Porteous, David J ; Horvath, Steve ; Lu, Ake T ; McIntosh, Andrew M ; Whalley, Heather C ; Marioni, Riccardo E
Greally, John M.
Assuntos: Age ; Aging ; Aging - genetics ; Aging - pathology ; Analysis ; Biology and Life Sciences ; Blood ; Brain research ; Dementia ; Deoxyribonucleic acid ; DNA ; DNA methylation ; DNA Methylation - genetics ; Epidemiology ; Epigenesis, Genetic ; Epigenetic inheritance ; Epigenetics ; Geffen, David ; Gene expression ; Gene Expression Regulation - genetics ; Genes ; Genetic Predisposition to Disease ; Genetic research ; Genetics ; Genome-wide association studies ; Genome-Wide Association Study ; Genomes ; Genomics ; Health aspects ; Humans ; Immune system ; Innate immunity ; Life span ; Longevity - genetics ; Medicine ; Meta-analysis ; Methylation ; Morbidity ; Mortality ; Novels ; Physical Sciences ; Physiological aspects ; Polymorphism, Single Nucleotide - genetics ; Proxy ; Psychiatry ; Research and Analysis Methods ; Single nucleotide polymorphisms ; Single-nucleotide polymorphism ; Supervision ; United Kingdom
É parte de: PLoS genetics, 2019-11, Vol.15 (11), p.e1008104-e1008104
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The authors have declared that no competing interests exist.
Descrição: '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.
Editor: United States: Public Library of Science
Idioma: Inglês

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A meta-analysis of genome-wide association studies of epigenetic age acceleration

United States: Public Library of Science

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