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Masahiro Miyake, Kenji Yamashiro, Hiroshi Tamura, Kyoko Kumagai, Masaaki Saito, Masako Sugahara-Kuroda, Munemitsu Yoshikawa, Maho Oishi, Yumiko Akagi-Kurashige, Isao Nakata, Hideo Nakanishi, Norimoto Gotoh, Akio Oishi, Fumihiko Matsuda, Ryo Yamada, Chiea-Chuen Khor, Yasuo Kurimoto, Tetsuju Sekiryu, Akitaka Tsujikawa, Nagahisa Yoshimura; The Contribution of Genetic Architecture to the 10-Year Incidence of Age-Related Macular Degeneration in the Fellow Eye. Invest. Ophthalmol. Vis. Sci. 2015;56(9):5353-5361. doi: https://doi.org/10.1167/iovs.14-16020.
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To correlate a genetic risk score based on age-related macular degeneration (AMD) susceptibility genes with the risk of AMD in the second eye.
This is a retrospective, open cohort study consisting of 891 unilateral AMD patients, who were followed for at least 12 months and recruited from three institutes. DNAs were genotyped using Illumina OmniExpress, HumanOmni2.5-8, and/or HumanExome. Survival analyses and Cox proportional hazard models were used to examine the association between 11 AMD susceptibility genes and the duration until second-eye involvement in 499 samples from Kyoto University, which were replicated in two other cohorts. Genetic risk score (GRS) was also evaluated.
The ARMS2 rs10490924 recessive model (hazard ratio [HR]meta = 2.04; Pmeta = 3.4 × 10−3) and CFH rs800292 additive model (HRmeta = 1.77; Pmeta = 0.013) revealed significant associations with second-eye involvement. The dominant model of TNFRSF10A rs13278062, VEGFA rs943080, and CFI rs4698775 showed consistent effects across three datasets (I2 = 0%; HRmeta = 1.46, 1.30, 1.51, respectively). The GRS using these five single nucleotide polymorphisms (SNPs) was also significantly associated (HRmeta [per score] = 2.42; P = 2.2 × 10−5; I2 = 0%). After 10 years from the first visit, the patients within the top 10% by GRS showed a 51% hazard rate, in contrast to 2.3% among patients within the lowest 10% by GRS.
We demonstrated that the GRS using ARMS2, CFH, TNFRSF10A, VEGFA, and CFI was significantly associated with second-eye involvement. Genetic risk has high predictive ability for second-eye involvement of AMD.
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