%0 Journal Article %J Invest Ophthalmol Vis Sci %D 2015 %T The Contribution of Genetic Architecture to the 10-Year Incidence of Age-Related Macular Degeneration in the Fellow Eye. %A Miyake, Masahiro %A Yamashiro, Kenji %A Tamura, Hiroshi %A Kumagai, Kyoko %A Saito, Masaaki %A Sugahara-Kuroda, Masako %A Yoshikawa, Munemitsu %A Oishi, Maho %A Akagi-Kurashige, Yumiko %A Nakata, Isao %A Nakanishi, Hideo %A Gotoh, Norimoto %A Oishi, Akio %A Matsuda, Fumihiko %A Yamada, Ryo %A Khor, Chiea-Chuen %A Kurimoto, Yasuo %A Sekiryu, Tetsuju %A Tsujikawa, Akitaka %A Yoshimura, Nagahisa %X

PURPOSE: To correlate a genetic risk score based on age-related macular degeneration (AMD) susceptibility genes with the risk of AMD in the second eye. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

%B Invest Ophthalmol Vis Sci %V 56 %P 5353-61 %8 2015 Aug 1 %G eng %N 9 %1 http://www.ncbi.nlm.nih.gov/pubmed/26275133?dopt=Abstract %R 10.1167/iovs.14-16020