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

Satoshi Arakawa; Atsushi Takahashi; Kyota Ashikawa; Naoya Hosono; Tomomi Aoi; Miho Yasuda; Yuji Oshima; Shigeo Yoshida; Hiroshi Enaida; Takashi Tsuchihashi; Keisuke Mori; Shigeru Honda; Akira Negi; Akira Arakawa; Kazuaki Kadonosono; Yutaka Kiyohara; Naoyuki Kamatani; Yusuke Nakamura; Tatsuro Ishibashi; Michiaki Kubo

doi:10.1038/ng.938

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

Satoshi Arakawa, Atsushi Takahashi, Kyota Ashikawa, Naoya Hosono, Tomomi Aoi, Miho Yasuda, Yuji Oshima, Shigeo Yoshida, Hiroshi Enaida, Takashi Tsuchihashi, Keisuke Mori, Shigeru Honda, Akira Negi, Akira Arakawa, Kazuaki Kadonosono, Yutaka Kiyohara, Naoyuki Kamatani, Yusuke Nakamura, Tatsuro Ishibashi, Michiaki Kubo

Research output: Contribution to journal › Article › peer-review

116 Citations (Scopus)

Abstract

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.

Original language	English
Pages (from-to)	1001-1005
Number of pages	5
Journal	Nature Genetics
Volume	43
Issue number	10
DOIs	https://doi.org/10.1038/ng.938
Publication status	Published - 10-2011
Externally published	Yes

All Science Journal Classification (ASJC) codes

Genetics

Access to Document

10.1038/ng.938

Cite this

Arakawa, S., Takahashi, A., Ashikawa, K., Hosono, N., Aoi, T., Yasuda, M., Oshima, Y., Yoshida, S., Enaida, H., Tsuchihashi, T., Mori, K., Honda, S., Negi, A., Arakawa, A., Kadonosono, K., Kiyohara, Y., Kamatani, N., Nakamura, Y., Ishibashi, T., & Kubo, M. (2011). Genome-wide association study identifies two susceptibility loci for exudative age-related macular degeneration in the Japanese population. Nature Genetics, 43(10), 1001-1005. https://doi.org/10.1038/ng.938

@article{dc956c54abbd427a8366b8ec99f7b44d,

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

abstract = "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.",

author = "Satoshi Arakawa and Atsushi Takahashi and Kyota Ashikawa and Naoya Hosono and Tomomi Aoi and Miho Yasuda and Yuji Oshima and Shigeo Yoshida and Hiroshi Enaida and Takashi Tsuchihashi and Keisuke Mori and Shigeru Honda and Akira Negi and Akira Arakawa and Kazuaki Kadonosono and Yutaka Kiyohara and Naoyuki Kamatani and Yusuke Nakamura and Tatsuro Ishibashi and Michiaki Kubo",

year = "2011",

month = oct,

doi = "10.1038/ng.938",

language = "English",

volume = "43",

pages = "1001--1005",

journal = "Nature Genetics",

issn = "1061-4036",

publisher = "Nature Publishing Group",

number = "10",

}

Arakawa, S, Takahashi, A, Ashikawa, K, Hosono, N, Aoi, T, Yasuda, M, Oshima, Y, Yoshida, S, Enaida, H, Tsuchihashi, T, Mori, K, Honda, S, Negi, A, Arakawa, A, Kadonosono, K, Kiyohara, Y, Kamatani, N, Nakamura, Y, Ishibashi, T & Kubo, M 2011, 'Genome-wide association study identifies two susceptibility loci for exudative age-related macular degeneration in the Japanese population', Nature Genetics, vol. 43, no. 10, pp. 1001-1005. https://doi.org/10.1038/ng.938

TY - JOUR

T1 - Genome-wide association study identifies two susceptibility loci for exudative age-related macular degeneration in the Japanese population

AU - Arakawa, Satoshi

AU - Takahashi, Atsushi

AU - Ashikawa, Kyota

AU - Hosono, Naoya

AU - Aoi, Tomomi

AU - Yasuda, Miho

AU - Oshima, Yuji

AU - Yoshida, Shigeo

AU - Enaida, Hiroshi

AU - Tsuchihashi, Takashi

AU - Mori, Keisuke

AU - Honda, Shigeru

AU - Negi, Akira

AU - Arakawa, Akira

AU - Kadonosono, Kazuaki

AU - Kiyohara, Yutaka

AU - Kamatani, Naoyuki

AU - Nakamura, Yusuke

AU - Ishibashi, Tatsuro

AU - Kubo, Michiaki

PY - 2011/10

Y1 - 2011/10

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=80053385445&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=80053385445&partnerID=8YFLogxK

U2 - 10.1038/ng.938

DO - 10.1038/ng.938

M3 - Article

C2 - 21909106

AN - SCOPUS:80053385445

SN - 1061-4036

VL - 43

SP - 1001

EP - 1005

JO - Nature Genetics

JF - Nature Genetics

IS - 10

ER -

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

Abstract

All Science Journal Classification (ASJC) codes

Access to Document

Other files and links

Fingerprint

Cite this