Methylome-wide association study of whole blood DNA in the Norfolk Island isolate identifies robust loci associated with age.

Abstract:

:Epigenetic regulation of various genomic functions, including gene expression, provide mechanisms whereby an organism can dynamically respond to changes in its environment and modify gene expression accordingly. One epigenetic mechanism implicated in human aging and age-related disorders is DNA methylation. Isolated populations such as Norfolk Island (NI) should be advantageous for the identification of epigenetic factors related to aging due to reduced genetic and environmental variation. Here we conducted a methylome-wide association study of age using whole blood DNA in 24 healthy female individuals from the NI genetic isolate (aged 24-47 years). We analysed 450K methylation array data using a machine learning approach (GLMnet) to identify age-associated CpGs. We identified 497 CpG sites, mapping to 422 genes, associated with age, with 11 sites previously associated with age. The strongest associations identified were for a single CpG site in MYOF and an extended region within the promoter of DDO. These hits were validated in curated public data from 2316 blood samples (MARMAL-AID). This study is the first to report robust age associations for MYOF and DDO, both of which have plausible functional roles in aging. This study also illustrates the value of genetic isolates to reveal new associations with epigenome-level data.

journal_name

Aging (Albany NY)

journal_title

Aging

authors

Benton MC,Sutherland HG,Macartney-Coxson D,Haupt LM,Lea RA,Griffiths LR

doi

10.18632/aging.101187

subject

Has Abstract

pub_date

2017-02-28 00:00:00

pages

753-768

issue

3

issn

1945-4589

pii

101187

journal_volume

9

pub_type

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