title: DNA methylation landscape of ocular tissue relative to matched peripheral blood.
abstract: Epigenetic variation is implicated in a range of non-communicable diseases, including those of the eye. However, investigating the role of epigenetic variation in central tissues, such as eye or brain, remains problematic and peripheral tissues are often used as surrogates. In this study, matched human blood and eye tissue (n = 8) were obtained post-mortem and DNA methylation profiling performed on blood, neurosensory retina, retinal pigment epithelium (RPE)/choroid and optic nerve tissue using the Illumina Infinium HumanMethylation450 platform. Unsupervised clustering and principal components analysis revealed tissue of origin as the main driver of methylation variation. Despite this, there was a strong correlation of methylation profiles between tissues with >255,000 CpG sites found to have similar methylation levels. An additional ~16,000 show similarity across ocular tissues only. A small proportion of probes showing inter-individual variation in blood co-varied with eye tissues within individuals, however much of this variation may be genetically driven. An improved understanding of the epigenetic landscape of the eye will have important implications for understanding eye disease. Despite a generally high correlation irrespective of origin, tissue type is the major driver of methylation variation, with only limited covariation between blood and any specific ocular tissue.
authors.affiliation: Lions Eye Institute, University of Western Australia, Centre for Ophthalmology and Visual Science, Perth, Australia.|Centre for Eye Research Australia, University of Melbourne, Royal Victorian Eye and Ear Hospital, Melbourne, Australia.|Menzies Research Institute Tasmania, School of Medicine, University of Tasmania, Hobart, Australia.
authors.forename: Alex W
authors.initials: AW
authors.lastname: Hewitt
authors.affiliation: Cancer and Disease Epigenetics, Murdoch Childrens Research Institute, Royal Children's Hospital, Australia.
authors.forename: Vania
authors.initials: V
authors.lastname: Januar
authors.affiliation: Cancer and Disease Epigenetics, Murdoch Childrens Research Institute, Royal Children's Hospital, Australia.
authors.forename: Alexandra
authors.initials: A
authors.lastname: Sexton-Oates
authors.affiliation: Department of Pathology, University of Melbourne, Australia.
authors.forename: Jihoon E
authors.initials: JE
authors.lastname: Joo
authors.affiliation: Lions Eye Institute, University of Western Australia, Centre for Ophthalmology and Visual Science, Perth, Australia.
authors.forename: Maria
authors.initials: M
authors.lastname: Franchina
authors.affiliation: Centre for Vision Research, Department of Ophthalmology and Westmead Millennium Institute, University of Sydney, Westmead, Australia.
authors.forename: Jie Jin
authors.initials: JJ
authors.lastname: Wang
authors.affiliation: Centre for Eye Research Australia, University of Melbourne, Royal Victorian Eye and Ear Hospital, Melbourne, Australia.
authors.forename: Helena
authors.initials: H
authors.lastname: Liang
authors.affiliation: Department of Ophthalmology, Flinders University, Flinders Medical Centre, Adelaide, South Australia, Australia.
authors.forename: Jamie E
authors.initials: JE
authors.lastname: Craig
authors.affiliation: Cancer and Disease Epigenetics, Murdoch Childrens Research Institute, Royal Children's Hospital, Australia.|Department of Paediatrics, University of Melbourne, Australia.
authors.forename: Richard
authors.initials: R
authors.lastname: Saffery
mesh_terms: D000328:Adult; D000368:Aged; D000704:Analysis of Variance; D019295:Computational Biology / Q000379:methods; D018899:CpG Islands; D019175:DNA Methylation; D044127:Epigenesis, Genetic; D005123:Eye / Q000378:metabolism*; D063990:Gene Ontology; D023281:Genomics / Q000379:methods; D006801:Humans; D008297:Male; D008875:Middle Aged; D058977:Molecular Sequence Annotation