Methylome-wide association study of whole blood DNA in the Norfolk Island isolate identifies robust loci associated with age
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Benton_2017_Ageing.pdf. |
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Description
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.
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ID Code: | 105629 | ||||||||
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Item Type: | Contribution to Journal (Journal Article) | ||||||||
Refereed: | Yes | ||||||||
ORCID iD: |
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Measurements or Duration: | 16 pages | ||||||||
Keywords: | DNA methylation, GLMnet, Norfolk Island, aging, epigenetics | ||||||||
DOI: | 10.18632/aging.101187 | ||||||||
ISSN: | 1945-4589 | ||||||||
Pure ID: | 33216098 | ||||||||
Divisions: | Past > QUT Faculties & Divisions > Faculty of Health Past > Institutes > Institute of Health and Biomedical Innovation |
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Funding: | |||||||||
Copyright Owner: | Consult author(s) regarding copyright matters | ||||||||
Copyright Statement: | This work is covered by copyright. Unless the document is being made available under a Creative Commons Licence, you must assume that re-use is limited to personal use and that permission from the copyright owner must be obtained for all other uses. If the document is available under a Creative Commons License (or other specified license) then refer to the Licence for details of permitted re-use. It is a condition of access that users recognise and abide by the legal requirements associated with these rights. If you believe that this work infringes copyright please provide details by email to qut.copyright@qut.edu.au | ||||||||
Deposited On: | 19 Apr 2017 03:13 | ||||||||
Last Modified: | 18 Jul 2024 20:41 |
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