title: 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 inMYOFand an extended region within the promoter ofDDO. These hits were validated in curated public data from 2316 blood samples (MARMAL-AID). This study is the first to report robust age associations forMYOFandDDO, 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.
authors.affiliation: Genomics Research Centre, Institute of Health and Biomedical Innovation, School of Biomedical Sciences, Queensland University of Technology, Kelvin Grove, Queensland, 4059, Australia.
authors.forename: Miles C
authors.initials: MC
authors.lastname: Benton
authors.affiliation: Genomics Research Centre, Institute of Health and Biomedical Innovation, School of Biomedical Sciences, Queensland University of Technology, Kelvin Grove, Queensland, 4059, Australia.
authors.forename: Heidi G
authors.initials: HG
authors.lastname: Sutherland
authors.affiliation: Kenepuru Science Centre, Institute of Environmental Science and Research, Wellington 5240, New Zealand.
authors.forename: Donia
authors.initials: D
authors.lastname: Macartney-Coxson
authors.affiliation: Genomics Research Centre, Institute of Health and Biomedical Innovation, School of Biomedical Sciences, Queensland University of Technology, Kelvin Grove, Queensland, 4059, Australia.
authors.forename: Larisa M
authors.initials: LM
authors.lastname: Haupt
authors.affiliation: Genomics Research Centre, Institute of Health and Biomedical Innovation, School of Biomedical Sciences, Queensland University of Technology, Kelvin Grove, Queensland, 4059, Australia.
authors.forename: Rodney A
authors.initials: RA
authors.lastname: Lea
authors.affiliation: Genomics Research Centre, Institute of Health and Biomedical Innovation, School of Biomedical Sciences, Queensland University of Technology, Kelvin Grove, Queensland, 4059, Australia.
authors.forename: Lyn R
authors.initials: LR
authors.lastname: Griffiths
mesh_terms: D000328:Adult; D000375:Aging / Q000235:genetics*; D002135:Calcium-Binding Proteins / Q000235:genetics*; D018899:CpG Islands / Q000235:genetics; D050804:D-Aspartate Oxidase / Q000235:genetics*; D004247:DNA / Q000097:blood; D019175:DNA Methylation / Q000235:genetics*; D044127:Epigenesis, Genetic; D005260:Female; D055106:Genome-Wide Association Study; D006801:Humans; D008542:Melanesia; D008565:Membrane Proteins / Q000235:genetics*; D008875:Middle Aged; D009124:Muscle Proteins / Q000235:genetics*; D055815:Young Adult
chemical_list: D002135:Calcium-Binding Proteins; C415584:MYOF protein, human; D008565:Membrane Proteins; D009124:Muscle Proteins; D004247:DNA; D050804:D-Aspartate Oxidase; C494102:DDO protein, human
keywords: DNA methylation; GLMnet; Norfolk Island; aging; epigenetics