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Christopher Hwang, Elvira Agron, Traci E Clemons, Tiarnan D L Keenan, Catherine A Cukras, Wai T Wong, Emily Y Chew; Genetic factors associated with reticular pseudodrusen in participants of the Age-Related Eye Disease Study 2 (AREDS2). Invest. Ophthalmol. Vis. Sci. 2019;60(9):1194.
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To determine genetic association with reticular pseudodrusen (RPD) in eyes of participants of the AREDS2 study.
The Age-Related Eye Disease Study 2 (AREDS2), a clinical trial of oral supplements, enrolled persons with intermediate AMD in either both eyes or one eye with late AMD in the fellow eye. Fundus autofluorescence (FAF) images were obtained in a subset of participants at baseline and annually, and RPD were identified by masked grading. Associations with SNPs in 6 risk alleles (CFH rs1061170, ARMS2 rs10490924, VEGF-A rs943080, C3 rs2230199, C2/CFB rs116503776 and rs114254831) as well as the total genetic risk score (GRS) which was determined from the 52 SNPs from 34 loci associated with AMD, were individually analyzed using logistic regression analysis adjusting for age, sex, smoking and correlation between eyes. A Bonferroni correction of P=.007 was applied.
A total of 2611 eyes of 1307 participants had FAF images and genetics data available. RPD was present in 772 (29.6%) eyes of 468 participants. The risk allele frequency of ARMS2 was significantly different between eyes with RPD versus those without (OR = 1.76, 95% CI: 1.36–2.29 for GT vs GG; OR = 1.94, 95% CI: 1.41–2.66 for TT vs GG). For CFH and C3, the association reached nominal significance but with the Bonferroni correction, these 2 risk alleles as well as the remaining SNPs were not significantly different from those without RPD. Increasing GRS groups were associated with increasing risk of RPD presence: OR = 1.53, 95%CI: 0.95–2.49, P=.831 for GRS group 1; OR = 1.73, 95%CI: 1.09—2.76, P=.021 for GRS group 2; OR = 2.53, 95%CI: 1.62–3.94, P<.001 for GRS group 3; OR = 2.78, 95%CI: 1.78–4.34, P<.001 for GRS group 4.
Analyses in this large cohort confirm previous associations made between the ARMS2 risk allele with RPD. Further associations with higher GRS and RPD presence are demonstrated. These genetic associations shed light on the molecular pathways leading to RPD development specifically and to AMD progression more generally.
This abstract was presented at the 2019 ARVO Annual Meeting, held in Vancouver, Canada, April 28 - May 2, 2019.
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