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DNA methylation outlier burden, health, and ageing in Generation Scotland and the Lothian Birth Cohorts of 1921 and 1936.
Seeboth, Anne; McCartney, Daniel L; Wang, Yunzhang; Hillary, Robert F; Stevenson, Anna J; Walker, Rosie M; Campbell, Archie; Evans, Kathryn L; McIntosh, Andrew M; Hägg, Sara; Deary, Ian J; Marioni, Riccardo E.
Afiliação
  • Seeboth A; Centre for Genomic and Experimental Medicine, Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh, EH4 2XU, UK.
  • McCartney DL; Centre for Genomic and Experimental Medicine, Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh, EH4 2XU, UK.
  • Wang Y; Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
  • Hillary RF; Centre for Genomic and Experimental Medicine, Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh, EH4 2XU, UK.
  • Stevenson AJ; Centre for Genomic and Experimental Medicine, Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh, EH4 2XU, UK.
  • Walker RM; Centre for Genomic and Experimental Medicine, Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh, EH4 2XU, UK.
  • Campbell A; Centre for Cognitive Ageing and Cognitive Epidemiology, University of Edinburgh, Edinburgh, EH8 9JZ, UK.
  • Evans KL; Centre for Genomic and Experimental Medicine, Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh, EH4 2XU, UK.
  • McIntosh AM; Centre for Genomic and Experimental Medicine, Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh, EH4 2XU, UK.
  • Hägg S; Centre for Cognitive Ageing and Cognitive Epidemiology, University of Edinburgh, Edinburgh, EH8 9JZ, UK.
  • Deary IJ; Centre for Genomic and Experimental Medicine, Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh, EH4 2XU, UK.
  • Marioni RE; Centre for Cognitive Ageing and Cognitive Epidemiology, University of Edinburgh, Edinburgh, EH8 9JZ, UK.
Clin Epigenetics ; 12(1): 49, 2020 03 26.
Article em En | MEDLINE | ID: mdl-32216821
BACKGROUND: DNA methylation outlier burden has been suggested as a potential marker of biological age. An outlier is typically defined as DNA methylation levels at any one CpG site that are three times beyond the inter-quartile range from the 25th or 75th percentiles compared to the rest of the population. DNA methylation outlier burden (the number of such outlier sites per individual) increases exponentially with age. However, these findings have been observed in small samples. RESULTS: Here, we showed an association between age and log10-transformed DNA methylation outlier burden in a large cross-sectional cohort, the Generation Scotland Family Health Study (N = 7010, ß = 0.0091, p < 2 × 10-16), and in two longitudinal cohort studies, the Lothian Birth Cohorts of 1921 (N = 430, ß = 0.033, p = 7.9 × 10-4) and 1936 (N = 898, ß = 0.0079, p = 0.074). Significant confounders of both cross-sectional and longitudinal associations between outlier burden and age included white blood cell proportions, body mass index (BMI), smoking, and batch effects. In Generation Scotland, the increase in epigenetic outlier burden with age was not purely an artefact of an increase in DNA methylation level variability with age (epigenetic drift). Log10-transformed DNA methylation outlier burden in Generation Scotland was not related to self-reported, or family history of, age-related diseases, and it was not heritable (SNP-based heritability of 4.4%, p = 0.18). Finally, DNA methylation outlier burden was not significantly related to survival in either of the Lothian Birth Cohorts individually or in the meta-analysis after correction for multiple testing (HRmeta = 1.12; 95% CImeta = [1.02; 1.21]; pmeta = 0.021). CONCLUSIONS: These findings suggest that, while it does not associate with ageing-related health outcomes, DNA methylation outlier burden does track chronological ageing and may also relate to survival. DNA methylation outlier burden may thus be useful as a marker of biological ageing.
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Texto completo: 1 Base de dados: MEDLINE Assunto principal: Envelhecimento / Metilação de DNA Tipo de estudo: Etiology_studies / Observational_studies / Prevalence_studies / Risk_factors_studies Limite: Adult / Female / Humans / Male / Middle aged País como assunto: Europa Idioma: En Ano de publicação: 2020 Tipo de documento: Article

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Envelhecimento / Metilação de DNA Tipo de estudo: Etiology_studies / Observational_studies / Prevalence_studies / Risk_factors_studies Limite: Adult / Female / Humans / Male / Middle aged País como assunto: Europa Idioma: En Ano de publicação: 2020 Tipo de documento: Article