title: Differential DNA methylation identified in the blood and retina of AMD patients.
abstract: Age-related macular degeneration (AMD) is a major cause of blindness in the western world. While genetic studies have linked both common and rare variants in genes involved in regulation of the complement system to increased risk of development of AMD, environmental factors, such as smoking and nutrition, can also significantly affect the risk of developing the disease and the rate of disease progression. Since epigenetics has been implicated in mediating, in part, the disease risk associated with some environmental factors, we investigated a possible epigenetic contribution to AMD. We performed genome-wide DNA methylation profiling of blood from AMD patients and controls. No differential methylation site reached genome-wide significance; however, when epigenetic changes in and around known GWAS-defined AMD risk loci were explored, we found small but significant DNA methylation differences in the blood of neovascular AMD patients near age-related maculopathy susceptibility 2 (ARMS2), a top-ranked GWAS locus preferentially associated with neovascular AMD. The methylation level of one of the CpG sites significantly correlated with the genotype of the risk SNP rs10490924, suggesting a possible epigenetic mechanism of risk. Integrating genome-wide DNA methylation analysis of retina samples with and without AMD together with blood samples, we further identified a consistent, replicable change in DNA methylation in the promoter region of protease serine 50 (PRSS50). These methylation changes may identify sites in novel genes that are susceptible to non-genetic factors known to contribute to AMD development and progression.
authors.affiliation: a Department of Ophthalmology; Johns Hopkins University; School of Medicine ; Baltimore , MD USA.
authors.forename: Verity F
authors.initials: VF
authors.lastname: Oliver
authors.forename: Andrew E
authors.initials: AE
authors.lastname: Jaffe
authors.forename: Jin
authors.initials: J
authors.lastname: Song
authors.forename: Guohua
authors.initials: G
authors.lastname: Wang
authors.forename: Pingwu
authors.initials: P
authors.lastname: Zhang
authors.forename: Kari E
authors.initials: KE
authors.lastname: Branham
authors.forename: Anand
authors.initials: A
authors.lastname: Swaroop
authors.forename: Charles G
authors.initials: CG
authors.lastname: Eberhart
authors.forename: Donald J
authors.initials: DJ
authors.lastname: Zack
authors.forename: Jiang
authors.initials: J
authors.lastname: Qian
authors.forename: Shannath L
authors.initials: SL
authors.lastname: Merbs
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D019175:DNA Methylation / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study; D005838:Genotype; D006801:Humans; D008268:Macular Degeneration / Q000097:blood / Q000235:genetics* / Q000473:pathology; D008297:Male; D020641:Polymorphism, Single Nucleotide; D012160:Retina / Q000378:metabolism / Q000473:pathology; D012307:Risk Factors
keywords: AMD, Age-related macular degeneration; AMD-MMAP, Michigan, Mayo; AREDS, Age-Related Eye Disease Study; AREDS, and Pennsylvania; DNA methylation; DNAm, DNA methylation; GA, geographic atrophy; GWAS, genome-wide association study; KEC, Kellogg Eye Center; LCLs, lymphoblastoid cell lines; NV, choroidal neovascularization; RPE, retinal pigment epithelium; age-related macular degeneration; genome-wide methylation; meQTL, methylation quantitative trait loci; methyl-QTL; peripheral blood leukocytes; retina