Genome-wide association study identifies two susceptibility loci for exudative age-related macular degeneration in the Japanese population

• Published in: Nature genetics Vol. 43; no. 10; pp. 1001 - 1004
• Main Authors: Kubo, Michiaki, Arakawa, Satoshi, Takahashi, Atsushi, Ashikawa, Kyota, Hosono, Naoya, Aoi, Tomomi, Yasuda, Miho, Oshima, Yuji, Yoshida, Shigeo, Enaida, Hiroshi, Tsuchihashi, Takashi, Mori, Keisuke, Honda, Shigeru, Negi, Akira, Arakawa, Akira, Kadonosono, Kazuaki, Kiyohara, Yutaka, Kamatani, Naoyuki, Nakamura, Yusuke, Ishibashi, Tatsuro
• Format: Journal Article
• Language: English
• Published: New York Nature Publishing Group US 01.10.2011; Nature Publishing Group
• Subjects: 631/208/205/2138; 631/208/727/2000; 631/378/1689/1626; Age Factors; Agriculture; Animal Genetics and Genomics; Apoptosis; Asian Continental Ancestry Group - genetics; Biological and medical sciences; Biomedical and Life Sciences; Biomedicine; Cancer Research; Case-Control Studies; Chromosomes; Chromosomes, Human, Pair 4 - genetics; Chromosomes, Human, Pair 8 - genetics; Confidence intervals; Development and progression; Disease susceptibility; Fundamental and applied biological sciences. Psychology; Gene Function; Genetic aspects; Genetic factors; Genetic Loci; Genetic Predisposition to Disease; Genetic research; Genetics of eukaryotes. Biological and molecular evolution; Genome, Human; Genome-Wide Association Study; Genomes; Genotype & phenotype; Human Genetics; Humans; letter; Logistic Models; Macular degeneration; Medical sciences; Nitric oxide; Odds Ratio; Older people; Ophthalmology; Pathogenesis; Physiological aspects; Polymorphism, Single Nucleotide; Principal components analysis; Retinopathies; Risk Factors; Wet Macular Degeneration - genetics; Japan; Age related macular degeneration; Eye disease; Identification; Retinopathy; Locus; Japanese
• ISSN: 1061-4036; 1546-1718
• DOI: 10.1038/ng.938

Age-related macular degeneration (AMD), the leading cause of irreversible blindness in the world, is a complex disease caused by multiple environmental and genetic risk factors. To identify genetic factors that modify the risk of exudative AMD in the Japanese population, we conducted a genome-wide association study and a replication study using a total of 1,536 individuals with exudative AMD and 18,894 controls. In addition to CFH (rs800292, P = 4.23 × 10−15) and ARMS2 (rs3750847, P = 8.67 × 10−29) loci, we identified two new susceptibility loci for exudative AMD: TNFRSF10A-LOC389641 on chromosome 8p21 (rs13278062, combined P = 1.03 × 10−12, odds ratio = 0.73) and REST-C4orf14-POLR2B-IGFBP7 on chromosome 4q12 (rs1713985, combined P = 2.34 × 10−8, odds ratio = 1.30). Fine mapping revealed that rs13278062, which is known to alter TNFRSF10A transcriptional activity, had the most significant association in 8p21 region. Our results provide new insights into the pathophysiology of exudative AMD.