July 2018
Volume 59, Issue 9
Open Access
ARVO Annual Meeting Abstract  |   July 2018
Genome-wide association study for response to ranibizumab therapy in 919 individuals with age-related macular degeneration
Author Affiliations & Notes
  • Masato Akiyama
    Laboratory for Statistical Analysis, RIKEN, Center for Integrative Medical Sciences, Yokohama, Kanagawa, Japan
    Department of Ophthalmology, Kyushu University, Fukuoka, Fukuoka, Japan
  • Atsushi Takahashi
    Laboratory for Statistical Analysis, RIKEN, Center for Integrative Medical Sciences, Yokohama, Kanagawa, Japan
    Laboratory for Omics Informatics, Omics Research Center, National Cerebral and Cardiovascular Center, Osaka, Japan
  • Yukihide Momozawa
    Laboratory for Genotyping Development, RIKEN Center for Integrative Medical Science, Yokohama, Japan
  • Satoshi Arakawa
    Department of Ophthalmology, Kyushu University, Fukuoka, Fukuoka, Japan
    Japan Community Health care Organization, Kyushu Hospital, Kitakyushu, Japan
  • Fuyuki Miya
    Laboratory for Medical Science Mathematics, RIKEN Center for Integrative Medical Science, Yokohama, Japan
    Department of Medical Science Mathematics, Medical Research Institute, Tokyo Medical and Dental University, Tokyo, Japan
  • Yuji Oshima
    Department of Ophthalmology, Kyushu University, Fukuoka, Fukuoka, Japan
    Department of Ophthalmology, Fukuoka University Chikushi Hospital, Fukuoka, Japan
  • Miho Yasuda
    Department of Ophthalmology, Kyushu University, Fukuoka, Fukuoka, Japan
  • Shigeo Yoshida
    Department of Ophthalmology, Kyushu University, Fukuoka, Fukuoka, Japan
  • Yasuo Yanagi
    Department of Ophthalmology, University of Tokyo School of Medicine, Tokyo, Japan
    Medical Retina Department, Singapore National Eye Center, Singapore , Japan
  • Koji Tanaka
    Division of Ophthalmology, Department of Visual Sciences, Nihon University School of Medicine, Tokyo, Japan
  • Yuichiro Ogura
    Department of Ophthalmology and Visual Science, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan
  • Kanji Takahashi
    Department of Ophthalmology, Kansai Medical University, Osaka, Japan
  • Kimihiko Fujisawa
    Japan Community Health care Organization, Kyushu Hospital, Kitakyushu, Japan
  • Kazuaki Kadonosono
    Department of Ophthalmology & Micro-technology, Yokohama City University Graduate School of Medicine, Yokohama, Japan
  • Tatsuro Ishibashi
    Department of Ophthalmology, Kyushu University, Fukuoka, Fukuoka, Japan
  • Koh-hei Sonoda
    Department of Ophthalmology, Kyushu University, Fukuoka, Fukuoka, Japan
  • Footnotes
    Commercial Relationships   Masato Akiyama, None; Atsushi Takahashi, None; Yukihide Momozawa, None; Satoshi Arakawa, None; Fuyuki Miya, None; Yuji Oshima, None; Miho Yasuda, None; Shigeo Yoshida, None; Yasuo Yanagi, None; Koji Tanaka, None; Yuichiro Ogura, None; Kanji Takahashi, None; Kimihiko Fujisawa, None; Kazuaki Kadonosono, None; Tatsuro Ishibashi, None; Koh-hei Sonoda, None
  • Footnotes
    Support  This study was funded in part by the BioBank Japan project supported by Ministry of Education, Sports, Science and Technology and Grants-in-Aid for Scientific Research from Japan Society for the Promotion of Science (Kakenhi 24249083).
Investigative Ophthalmology & Visual Science July 2018, Vol.59, 1426. doi:https://doi.org/
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    • Get Citation

      Masato Akiyama, Atsushi Takahashi, Yukihide Momozawa, Satoshi Arakawa, Fuyuki Miya, Yuji Oshima, Miho Yasuda, Shigeo Yoshida, Yasuo Yanagi, Koji Tanaka, Yuichiro Ogura, Kanji Takahashi, Kimihiko Fujisawa, Kazuaki Kadonosono, Tatsuro Ishibashi, Koh-hei Sonoda; Genome-wide association study for response to ranibizumab therapy in 919 individuals with age-related macular degeneration. Invest. Ophthalmol. Vis. Sci. 2018;59(9):1426. doi: https://doi.org/.

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      © ARVO (1962-2015); The Authors (2016-present)

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Abstract

Purpose : Although anti-vascular endothelial growth factor (VEGF) agents improved visual acuity in patients with exudative age-related macular degeneration (AMD), genetic factors associated with treatment outcomes have been largely unknown. To investigate genetic factors influencing visual outcome with ranibizumab therapy, we conducted a genome-wide association study (GWAS) and a replication study in a Japanese population.

Methods : Treatment response was determined based on the change in visual acuity at 3 months. We defined individuals who maintained or improved their best-corrected visual acuity (BCVA) as responders, and individuals whose BCVA worsened as non-responders. We performed a genome-wide association study (GWAS) in 434 individuals who were treated with intravitreal ranibizumab using 6,826,359 single nucleotide polymorphisms (SNPs). We selected 93 variants showing P < 1.0×10-4 in GWAS, and genotyped them in an independent set of 487 individuals with AMD.

Results : Among the participants, 195 participants (21.2%) were defined as non-responders. In the combined analysis of GWAS and a replication study, we did not observe variants which showed genome-wide significant association. However, four SNPs showed suggestive levels of associations with the visual outcome (rs17822656, rs76150532, rs17296444, and rs75165563: Pcombined < 1.0×10-5). The frequencies of these SNPs were low in responders and were more than 2-fold higher in non-responders. The proportions of non-responders were 13.7%, 38.8%, 58.0%, and 80.0% in individuals with 0, 1, 2, and 3 or more risk alleles, respectively. Changes in BCVA at 3 months decreased linearly as the number of risk alleles increased (P = 1.67 × 10-12). The area under the curve using age, baseline best-corrected visual acuity, and history of previous treatment was 0.607, and improved significantly to 0.713 in combination with identified SNPs (P < 0.0001).

Conclusions : Although further evaluations are needed, our results suggest four candidate variants influencing response to ranibizumab therapy.

This is an abstract that was submitted for the 2018 ARVO Annual Meeting, held in Honolulu, Hawaii, April 29 - May 3, 2018.

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