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Elisa van Leeuwen, Johanna Maria Colijn, Andre G. Uitterlinden, Joyce van Meurs, Albert Hofman, Johannes R Vingerling, Caroline Klaver; Methylation profiles in age-related macular degeneration. Invest. Ophthalmol. Vis. Sci. 2017;58(8):1843.
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Genome-wide association studies (GWAS) have successfully identified loci associated with age-related macular degeneration (AMD), however, only 27.2% of the disease variability is explained by the 52 variants discovered in the latest and largest GWAS. These variants function within pathways that lead to AMD, however not all pathways involved in AMD are known. We investigated whether DNA methylation is associated with AMD and to discover more implicated pathways in the disease process.
Using the Illumina Human Methylation 450K array platform, we assessed the DNA methylation levels of 419,938 CpG sites in whole blood across 1,472 individuals of the Rotterdam Study (RS) I, RS-II and RS-III. We performed an epigenomic wide association study (EWAS) in individuals with AMD versus non-affected 60+ year old controls adjusting for age and gender.
A total of 594 individuals with AMD and 448 controls were available for this analysis. No methylated sites were epigenome-wide significant (p-value<1.00x10-7), but 2 were suggestive (p-value<1.00x10-5). We did not found any significant methylated sites in any of the genes that have been identified before in association with AMD. The lowest P-value was observed for a methylated probe within the LRAT gene (p-value=7.56x10-7), a gene implicated in Leber’s congenital amaurosis. The top ten methylated sites were in genes which are expressed in the retina.
Our data suggest that methylation may play a role in AMD and that epigenetic analyses may reveal new pathways. This hypothesis generating exercise has shown that the association between DNA methylation and AMD should be investigated and therefore larger data sets of methylation profiles, especially in retina samples are needed to draw more profound conclusions.
This is an abstract that was submitted for the 2017 ARVO Annual Meeting, held in Baltimore, MD, May 7-11, 2017.
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