TY - JOUR
T1 - Differential DNA methylation identified in the blood and retina of AMD patients
AU - Oliver, Verity F.
AU - Jaffe, Andrew E.
AU - Song, Jin
AU - Wang, Guohua
AU - Zhang, Pingwu
AU - Branham, Kari E.
AU - Swaroop, Anand
AU - Eberhart, Charles G.
AU - Zack, Donald J.
AU - Qian, Jiang
AU - Merbs, Shannath L.
N1 - Funding Information:
This work was supported by the National Institutes of Health [R01EY020406 to SLM, R01EY023188 to SLM and JQ, R01EY024580 to JQ]; the National Eye Institute Core Grant [P30EY001765]; the Intramural Research Program of the National Eye Institute (to AS); Foundation Fighting Blindness (to KEB); the generosity of Agnes Nixon (SLM). The collection of the Michigan AMD-MMAP cohort was funded by the National Eye Institute [EY016862 to AS]. Illumina Human Methylation 450K profiling was performed by the Center for Inherited Disease Research (CIDR) through the NEI grant X01HG006605.
Publisher Copyright:
© 2015 Taylor and Francis Group, LLC.
PY - 2015/1/1
Y1 - 2015/1/1
N2 - 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.
AB - 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.
KW - Age-related macular degeneration
KW - DNA methylation
KW - Genome-wide methylation
KW - Methyl-QTL
KW - Peripheral blood leukocytes
KW - Retina
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U2 - 10.1080/15592294.2015.1060388
DO - 10.1080/15592294.2015.1060388
M3 - Article
C2 - 26067391
AN - SCOPUS:84943773700
VL - 10
SP - 698
EP - 707
JO - Epigenetics
JF - Epigenetics
SN - 1559-2294
IS - 8
ER -