Abstract
To identify factors associated with ranibizumab responses in patients with exudative age-related macular degeneration (AMD), we performed a genome-wide association study (GWAS) and a replication study using a total of 919 exudative AMD patients treated with intravitreal ranibizumab in a Japanese population. In the combined analysis of GWAS and the replication study, no loci reached genome-wide significant level; however, we found four variants showed suggestive level of associations with visual loss at month three (rs17822656, rs76150532, rs17296444, and rs75165563: Pcombined < 1.0 × 10−5). Of the candidate genes within these loci, three were relevant to VEGF-related pathway (KCNMA1, SOCS2, and OTX2). The proportions of patients who worsened visual acuity were 13.7%, 38.8%, 58.0%, and 80.0% in patients with 0, 1, 2, and 3 or more identified risk variants, respectively. Changes in visual acuity decreased linearly as the number of risk variants increased (P = 1.67 × 10–12). The area under the curve using age, baseline visual acuity, and history of previous treatment was 0.607, and improved significantly to 0.713 in combination with identified variants (P < 0.0001). Although further study is needed to confirm their associations, our results offer candidate variants influencing response to ranibizumab therapy.
| Original language | English |
|---|---|
| Pages (from-to) | 1083-1091 |
| Number of pages | 9 |
| Journal | Journal of Human Genetics |
| Volume | 63 |
| Issue number | 10 |
| DOIs | |
| Publication status | Published - Oct 1 2018 |
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All Science Journal Classification (ASJC) codes
- Genetics
- Genetics(clinical)
Cite this
Genome-wide association study suggests four variants influencing outcomes with ranibizumab therapy in exudative age-related macular degeneration. / Akiyama, Masato; Takahashi, Atsushi; Momozawa, Yukihide; Arakawa, Satoshi; Miya, Fuyuki; Tsunoda, Tatsuhiko; Ashikawa, Kyota; Oshima, Yuji; Yasuda, Miho; Yoshida, Shigeo; Enaida, Hiroshi; Tan, Xue; Yanagi, Yasuo; Yasukawa, Tsutomu; Ogura, Yuichiro; Nagai, Yoshimi; Takahashi, Kanji; Fujisawa, Kimihiko; Inoue, Maiko; Arakawa, Akira; Tanaka, Koji; Yuzawa, Mitsuko; Kadonosono, Kazuaki; Sonoda, Koh Hei; Ishibashi, Tatsuro; Kubo, Michiaki.
In: Journal of Human Genetics, Vol. 63, No. 10, 01.10.2018, p. 1083-1091.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Genome-wide association study suggests four variants influencing outcomes with ranibizumab therapy in exudative age-related macular degeneration
AU - Akiyama, Masato
AU - Takahashi, Atsushi
AU - Momozawa, Yukihide
AU - Arakawa, Satoshi
AU - Miya, Fuyuki
AU - Tsunoda, Tatsuhiko
AU - Ashikawa, Kyota
AU - Oshima, Yuji
AU - Yasuda, Miho
AU - Yoshida, Shigeo
AU - Enaida, Hiroshi
AU - Tan, Xue
AU - Yanagi, Yasuo
AU - Yasukawa, Tsutomu
AU - Ogura, Yuichiro
AU - Nagai, Yoshimi
AU - Takahashi, Kanji
AU - Fujisawa, Kimihiko
AU - Inoue, Maiko
AU - Arakawa, Akira
AU - Tanaka, Koji
AU - Yuzawa, Mitsuko
AU - Kadonosono, Kazuaki
AU - Sonoda, Koh Hei
AU - Ishibashi, Tatsuro
AU - Kubo, Michiaki
PY - 2018/10/1
Y1 - 2018/10/1
N2 - To identify factors associated with ranibizumab responses in patients with exudative age-related macular degeneration (AMD), we performed a genome-wide association study (GWAS) and a replication study using a total of 919 exudative AMD patients treated with intravitreal ranibizumab in a Japanese population. In the combined analysis of GWAS and the replication study, no loci reached genome-wide significant level; however, we found four variants showed suggestive level of associations with visual loss at month three (rs17822656, rs76150532, rs17296444, and rs75165563: Pcombined < 1.0 × 10−5). Of the candidate genes within these loci, three were relevant to VEGF-related pathway (KCNMA1, SOCS2, and OTX2). The proportions of patients who worsened visual acuity were 13.7%, 38.8%, 58.0%, and 80.0% in patients with 0, 1, 2, and 3 or more identified risk variants, respectively. Changes in visual acuity decreased linearly as the number of risk variants increased (P = 1.67 × 10–12). The area under the curve using age, baseline visual acuity, and history of previous treatment was 0.607, and improved significantly to 0.713 in combination with identified variants (P < 0.0001). Although further study is needed to confirm their associations, our results offer candidate variants influencing response to ranibizumab therapy.
AB - To identify factors associated with ranibizumab responses in patients with exudative age-related macular degeneration (AMD), we performed a genome-wide association study (GWAS) and a replication study using a total of 919 exudative AMD patients treated with intravitreal ranibizumab in a Japanese population. In the combined analysis of GWAS and the replication study, no loci reached genome-wide significant level; however, we found four variants showed suggestive level of associations with visual loss at month three (rs17822656, rs76150532, rs17296444, and rs75165563: Pcombined < 1.0 × 10−5). Of the candidate genes within these loci, three were relevant to VEGF-related pathway (KCNMA1, SOCS2, and OTX2). The proportions of patients who worsened visual acuity were 13.7%, 38.8%, 58.0%, and 80.0% in patients with 0, 1, 2, and 3 or more identified risk variants, respectively. Changes in visual acuity decreased linearly as the number of risk variants increased (P = 1.67 × 10–12). The area under the curve using age, baseline visual acuity, and history of previous treatment was 0.607, and improved significantly to 0.713 in combination with identified variants (P < 0.0001). Although further study is needed to confirm their associations, our results offer candidate variants influencing response to ranibizumab therapy.
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UR - http://www.scopus.com/inward/citedby.url?scp=85050930610&partnerID=8YFLogxK
U2 - 10.1038/s10038-018-0493-0
DO - 10.1038/s10038-018-0493-0
M3 - Article
C2 - 30054556
AN - SCOPUS:85050930610
VL - 63
SP - 1083
EP - 1091
JO - Journal of Human Genetics
JF - Journal of Human Genetics
SN - 1434-5161
IS - 10
ER -