DOI: 10.1101/19010728Nov 2, 2019Paper

DNA methylation outlier burden, health and ageing in Generation Scotland and the Lothian Birth Cohorts of 1921 and 1936.

MedRxiv : the Preprint Server for Health Sciences
Anne SeebothRiccardo E Marioni

Abstract

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. 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=7,010, {beta}=0.0091, p<2x10-16), and in two longitudinal cohort studies, the Lothian Birth Cohorts of 1921 (N=430, {beta}=0.033, p=7.9x10-4) and 1936 (N=898, {beta}=7.9x10-3, p=0.074). Significant confounders of both cross-sectional and longitudinal associations between outlier burden and age included white blood cell proportions, 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 burde...Continue Reading

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