@article {509176,
	title = {The Contribution of Genetic Architecture to the 10-Year Incidence of Age-Related Macular Degeneration in the Fellow Eye.},
	journal = {Invest Ophthalmol Vis Sci},
	volume = {56},
	number = {9},
	year = {2015},
	month = {2015 Aug 1},
	pages = {5353-61},
	abstract = {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 {\texttimes} 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 {\texttimes} 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.},
	issn = {1552-5783},
	doi = {10.1167/iovs.14-16020},
	author = {Miyake, Masahiro and Yamashiro, Kenji and Tamura, Hiroshi and Kumagai, Kyoko and Saito, Masaaki and Sugahara-Kuroda, Masako and Yoshikawa, Munemitsu and Oishi, Maho and Akagi-Kurashige, Yumiko and Nakata, Isao and Nakanishi, Hideo and Gotoh, Norimoto and Oishi, Akio and Matsuda, Fumihiko and Yamada, Ryo and Khor, Chiea-Chuen and Kurimoto, Yasuo and Sekiryu, Tetsuju and Tsujikawa, Akitaka and Yoshimura, Nagahisa}
}
