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

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Nature Genetics
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Published online

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.

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Gene Expression Omnibus


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Author information


  1. Laboratory for Genotyping Development, Center for Genomic Medicine, RIKEN Yokohama Institute, Yokohama, Japan.

    • Satoshi Arakawa,
    • Kyota Ashikawa,
    • Naoya Hosono,
    • Tomomi Aoi &
    • Michiaki Kubo
  2. Department of Ophthalmology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.

    • Satoshi Arakawa,
    • Miho Yasuda,
    • Yuji Oshima,
    • Shigeo Yoshida,
    • Hiroshi Enaida &
    • Tatsuro Ishibashi
  3. Laboratory for Statistical Analysis, Center for Genomic Medicine, RIKEN Yokohama Institute, Yokohama, Japan.

    • Atsushi Takahashi &
    • Naoyuki Kamatani
  4. Department of Ophthalmology, Saitama Medical University, Saitama, Japan.

    • Takashi Tsuchihashi &
    • Keisuke Mori
  5. Department of Surgery, Division of Ophthalmology, Kobe University Graduate School of Medicine, Kobe, Japan.

    • Shigeru Honda &
    • Akira Negi
  6. Department of Ophthalmology, Yokohama City University Medical Center, Yokohama, Japan.

    • Akira Arakawa &
    • Kazuaki Kadonosono
  7. Department of Environmental Medicine, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.

    • Yutaka Kiyohara
  8. Laboratory of Molecular Medicine, Human Genome Center, Institute of Medical Science, University of Tokyo, Tokyo, Japan.

    • Yusuke Nakamura


S.A., T.I., Y.N. and M.K. designed the study. S.A., N.H., K.A., T.A. and M.K. performed genotyping. S.A. and M.K. wrote the manuscript. A.T. performed statistical analysis at the genome-wide phase. Y.N. and M.K. managed DNA samples belonging to BioBank Japan. T.I. and Y.N. obtained funding for the study. M.Y., Y.O., S.Y. and H.E. collected GWAS samples. T.T., K.M., S.H., A.N., A.A. and K.K. collected case samples for the replication study. Y.K., N.K., Y.N. and M.K. supervised the study.

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