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Kenji Yamashiro, Masahiro Miyake, Munemitsu Yoshikawa, Isao Nakata, Hideo Nakanishi, Yumiko Akagi, Kyoko Kumagai, Maho Oishi, Akitaka Tsujikawa, Nagahisa Yoshimura; Susceptibility genes for large drusen in Japanese. Invest. Ophthalmol. Vis. Sci. 2014;55(13):2228.
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© ARVO (1962-2015); The Authors (2016-present)
Large drusen, typical characteristics of early age-related macular degeneration (AMD), is a great risk for developing vision-threatening late AMD. Although susceptibility genes for late AMD have been indentified in previous studies, genetic background of large drusen is still unclear. We evaluated associations between large drusen and known 24 regions associated with late AMD, using Japanese individuals recruited from the Nagahama Prospective Genome Cohort for the Comprehensive Human Bioscience (The Nagahama Study).
Among the participants with age ≥50 years old, 1224 were analyzed for drusen in their funds photograph and genotyped using Illumina HumanOmni2.5M or HumanHap610K. After imputation based on 1000 Genomes Project data and our standard quality control, 2509 single nucleotide polymorphisms (SNPs) in the 24 gene regions were included for the analysis. The association between large drusen and each SNP was evaluated by logistic regression analysis correcting for age and sex, and the associations between the AMD susceptibility genes and large drusen were analyzed by Versatile Gene-based Association Study (VEGAS; http://gump.qimr.edu.au/VEGAS/). To correct multiple comparison, false discovery rate was calculated.
Large drusen was observed in 377 participants, while 837 did not have large drusen in their both eyes. Among the 24 AMD susceptibility regions, CFI, C3, LIPC, APOE, and TGFBR1 showed P-value less than 0.05 in their top-10% SNPs test. False discovery rate was 0.108 for these 5 genes. In contrast to the strong association of CFH and ARMS2/HTRA1 to late AMD, these genes did not show significant association to large drusen; P-value was 0.11 for CFH, 0.18 for ARMS2, and 0.21 for HTRA1.
Formation of large drusen will be dependent on complement pathway and lipid metabolism pathway. ARMS2/HTRA1 would play its major roles in the late stage of AMD rather than in its early stage.
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