April 2014
Volume 55, Issue 13
Free
ARVO Annual Meeting Abstract  |   April 2014
Blood DNA Methylation Analysis Reveals Differential Methylation in AMD
Author Affiliations & Notes
  • Shannath L Merbs
    Wilmer Eye Institute, Johns Hopkins University School of Medicine, Baltimore, MD
  • Verity Frances Oliver
    Wilmer Eye Institute, Johns Hopkins University School of Medicine, Baltimore, MD
  • Andrew Jaffe
    Lieber Institute for Brain Development, Baltimore, MD
  • Anand Swaroop
    National Eye Institute, Bethesda, MD
  • Kari E Branham
    Kellogg Eye Center, University of Michigan, Ann Arbor, MI
  • Elizabeth Campochiaro
    Wilmer Eye Institute, Johns Hopkins University School of Medicine, Baltimore, MD
  • Donald J Zack
    Wilmer Eye Institute, Johns Hopkins University School of Medicine, Baltimore, MD
  • Jiang Qian
    Wilmer Eye Institute, Johns Hopkins University School of Medicine, Baltimore, MD
  • Footnotes
    Commercial Relationships Shannath Merbs, None; Verity Oliver, None; Andrew Jaffe, None; Anand Swaroop, None; Kari Branham, None; Elizabeth Campochiaro, None; Donald Zack, None; Jiang Qian, None
  • Footnotes
    Support None
Investigative Ophthalmology & Visual Science April 2014, Vol.55, 4996. doi:
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    • Get Citation

      Shannath L Merbs, Verity Frances Oliver, Andrew Jaffe, Anand Swaroop, Kari E Branham, Elizabeth Campochiaro, Donald J Zack, Jiang Qian; Blood DNA Methylation Analysis Reveals Differential Methylation in AMD. Invest. Ophthalmol. Vis. Sci. 2014;55(13):4996.

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      © ARVO (1962-2015); The Authors (2016-present)

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Abstract
 
Purpose
 

Age-related macular degeneration (AMD) is a leading cause of blindness worldwide. Genome wide association studies (GWAS) have successfully identified risk alleles, yet a large proportion of disease is not explained by these loci. Adverse environmental exposures, such as smoking, are known to increase an individual’s risk of AMD independent of genetic risk. We hypothesized that epigenetic factors, specifically aberrant DNA methylation, contribute to the development or progression of AMD.

 
Methods
 

Genome-wide DNA methylation analysis was performed by CIDR on trios of peripheral blood samples of patients with geographic atrophy (GA; n=100), neovascularization (NV, n=100) and sex- and age-matched controls (within 1 year, n=100) using the Infinium HumanMethylation450 BeadChip. These samples comprised part of the AMD-MMAP (Michigan, Mayo, AREDS, Pennsylvania) GWAS. Methylated (M) and unmethylated (U) channel intensities were normalized separately using a modified version of quantile normalization in the minfi Bioconductor package.

 
Results
 

Using a cutoff of p<10E-5, 16 genes in the NV group and 9 genes in the GA group contained at least 1 differentially methylated probe (DMP) compared to the control group. One of the genes that were in the NV group, which was not in the GA group, contained 2 significant DMPs in ARMS2, a gene previously implicated in AMD by GWAS. The top 2 DMPs in the GA group were within one gene, ENTPD1. When the cutoff was lowered to p<0.01, 11 of the 28 genes associated with the 19 SNP risk alleles contained at least one DMP in both groups combined. The IL17RC promoter, which had previously been identified as differentially methylated in peripheral monocytes of AMD patients, was not differentially methylated in these samples.

 
Conclusions
 

Through global methylation analysis, we identified new genes that may be associated with AMD, including for the first time a gene preferentially associated with GA. We also found a significant overlap between differentially methylated genes in peripheral blood and candidate genes from GWAS analyses such as ARMS2. Methylation changes in the blood may be useful for AMD biomarkers. Future work will include the integration of the genotypic and epigenetic data.

 
Keywords: 412 age-related macular degeneration  
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