New loci and coding variants confer risk for age-related macular degeneration in East Asians

Ching Yu Cheng; Kenji Yamashiro; Li Jia Chen; Jeeyun Ahn; Lulin Huang; Lvzhen Huang; Chui Ming G. Cheung; Masahiro Miyake; Peter D. Cackett; Ian Y. Yeo; Augustinus Laude; Ranjana Mathur; Junxiong Pang; Kar Seng Sim; Adrian H. Koh; Peng Chen; Shu Yen Lee; Doric Wong; Choi Mun Chan; Boon Kwang Loh; Yaoyao Sun; Sonia Davila; Isao Nakata; Hideo Nakanishi; Yumiko Akagi-Kurashige; Norimoto Gotoh; Akitaka Tsujikawa; Fumihiko Matsuda; Keisuke Mori; Shin Yoneya; Yoichi Sakurada; Hiroyuki Iijima; Tomohiro Iida; Shigeru Honda; Timothy Yuk Yau Lai; Pancy Oi Sin Tam; Haoyu Chen; Shibo Tang; Xiaoyan Ding; Feng Wen; Fang Lu; Xiongze Zhang; Yi Shi; Peiquan Zhao; Bowen Zhao; Jinghong Sang; Bo Gong; Rajkumar Dorajoo; Jian Min Yuan; Woon Puay Koh; Rob M. Van Dam; Yechiel Friedlander; Ying Lin; Martin L. Hibberd; Jia Nee Foo; Ningli Wang; Chang Hua Wong; Gavin S. Tan; Sang Jun Park; Mayuri Bhargava; Lingam Gopal; Thet Naing; Jiemin Liao; Peng Guan Ong; Paul Mitchell; Peng Zhou; Xuefeng Xie; Jinlong Liang; Junpu Mei; Xin Jin; Seang Mei Saw; Mineo Ozaki; Takanori Mizoguchi; Yasuo Kurimoto; Se Joon Woo; Hum Chung; Hyeong Gon Yu; Joo Young Shin; Dong Ho Park; In Taek Kim; Woohyok Chang; Min Sagong; Sang Joon Lee; Hyun Woong Kim; Ji Eun Lee; Yi Li; Jianjun Liu; Yik Ying Teo; Chew Kiat Heng; Tock Han Lim; Suk Kyun Yang; Kyuyoung Song; Eranga N. Vithana; Tin Aung; Jin Xin Bei; Yi Xin Zeng; E. Shyong Tai; Xiao Xin Li; Zhenglin Yang; Kyu Hyung Park; Chi Pui Pang; Nagahisa Yoshimura; Tien Yin Wong; Chiea Chuen Khor

doi:10.1038/ncomms7063

New loci and coding variants confer risk for age-related macular degeneration in East Asians

Ching Yu Cheng, Kenji Yamashiro, Li Jia Chen, Jeeyun Ahn, Lulin Huang, Lvzhen Huang, Chui Ming G. Cheung, Masahiro Miyake, Peter D. Cackett, Ian Y. Yeo, Augustinus Laude, Ranjana Mathur, Junxiong Pang, Kar Seng Sim, Adrian H. Koh, Peng Chen, Shu Yen Lee, Doric Wong, Choi Mun Chan, Boon Kwang LohYaoyao Sun, Sonia Davila, Isao Nakata, Hideo Nakanishi, Yumiko Akagi-Kurashige, Norimoto Gotoh, Akitaka Tsujikawa, Fumihiko Matsuda, Keisuke Mori, Shin Yoneya, Yoichi Sakurada, Hiroyuki Iijima, Tomohiro Iida, Shigeru Honda, Timothy Yuk Yau Lai, Pancy Oi Sin Tam, Haoyu Chen, Shibo Tang, Xiaoyan Ding, Feng Wen, Fang Lu, Xiongze Zhang, Yi Shi, Peiquan Zhao, Bowen Zhao, Jinghong Sang, Bo Gong, Rajkumar Dorajoo, Jian Min Yuan, Woon Puay Koh, Rob M. Van Dam, Yechiel Friedlander, Ying Lin, Martin L. Hibberd, Jia Nee Foo, Ningli Wang, Chang Hua Wong, Gavin S. Tan, Sang Jun Park, Mayuri Bhargava, Lingam Gopal, Thet Naing, Jiemin Liao, Peng Guan Ong, Paul Mitchell, Peng Zhou, Xuefeng Xie, Jinlong Liang, Junpu Mei, Xin Jin, Seang Mei Saw, Mineo Ozaki, Takanori Mizoguchi, Yasuo Kurimoto, Se Joon Woo, Hum Chung, Hyeong Gon Yu, Joo Young Shin, Dong Ho Park, In Taek Kim, Woohyok Chang, Min Sagong, Sang Joon Lee, Hyun Woong Kim, Ji Eun Lee, Yi Li, Jianjun Liu, Yik Ying Teo, Chew Kiat Heng, Tock Han Lim, Suk Kyun Yang, Kyuyoung Song, Eranga N. Vithana, Tin Aung, Jin Xin Bei, Yi Xin Zeng, E. Shyong Tai, Xiao Xin Li, Zhenglin Yang, Kyu Hyung Park, Chi Pui Pang, Nagahisa Yoshimura, Tien Yin Wong, Chiea Chuen Khor

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Abstract

Age-related macular degeneration (AMD) is a major cause of blindness, but presents differently in Europeans and Asians. Here, we perform a genome-wide and exome-wide association study on 2,119 patients with exudative AMD and 5,691 controls, with independent replication in 4,226 patients and 10,289 controls, all of East Asian descent, as part of The Genetics of AMD in Asians (GAMA) Consortium. We find a strong association between CETP Asp442Gly (rs2303790), an East Asian-specific mutation, and increased risk of AMD (odds ratio (OR)=1.70, P=5.60 × 10^-22). The AMD risk allele (442Gly), known to protect from coronary heart disease, increases HDL cholesterol levels by 0.17mmoll^-1 (P=5.82 × 10^-21) in East Asians (n=7,102). We also identify three novel AMD loci: C6orf223 Ala231Ala (OR=0.78, P=6.19 × 10^-18), SLC44A4 Asp47Val (OR=1.27, P=1.08 × 10^-11) and FGD6 Gln257Arg (OR=0.87, P=2.85 × 10^-8). Our findings suggest that some of the genetic loci conferring AMD susceptibility in East Asians are shared with Europeans, yet AMD in East Asians may also have a distinct genetic signature.

Original language	English
Article number	6063
Journal	Nature Communications
Volume	6
DOIs	https://doi.org/10.1038/ncomms7063
State	Published - 28 Jan 2015

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Cheng, C. Y., Yamashiro, K., Jia Chen, L., Ahn, J., Huang, L., Huang, L., Cheung, C. M. G., Miyake, M., Cackett, P. D., Yeo, I. Y., Laude, A., Mathur, R., Pang, J., Sim, K. S., Koh, A. H., Chen, P., Lee, S. Y., Wong, D., Chan, C. M., ... Khor, C. C. (2015). New loci and coding variants confer risk for age-related macular degeneration in East Asians. Nature Communications, 6, Article 6063. https://doi.org/10.1038/ncomms7063

@article{daf9209bd57f40a2b302c2f275b70238,

title = "New loci and coding variants confer risk for age-related macular degeneration in East Asians",

abstract = "Age-related macular degeneration (AMD) is a major cause of blindness, but presents differently in Europeans and Asians. Here, we perform a genome-wide and exome-wide association study on 2,119 patients with exudative AMD and 5,691 controls, with independent replication in 4,226 patients and 10,289 controls, all of East Asian descent, as part of The Genetics of AMD in Asians (GAMA) Consortium. We find a strong association between CETP Asp442Gly (rs2303790), an East Asian-specific mutation, and increased risk of AMD (odds ratio (OR)=1.70, P=5.60 × 10-22). The AMD risk allele (442Gly), known to protect from coronary heart disease, increases HDL cholesterol levels by 0.17mmoll-1 (P=5.82 × 10-21) in East Asians (n=7,102). We also identify three novel AMD loci: C6orf223 Ala231Ala (OR=0.78, P=6.19 × 10-18), SLC44A4 Asp47Val (OR=1.27, P=1.08 × 10-11) and FGD6 Gln257Arg (OR=0.87, P=2.85 × 10-8). Our findings suggest that some of the genetic loci conferring AMD susceptibility in East Asians are shared with Europeans, yet AMD in East Asians may also have a distinct genetic signature.",

author = "Cheng, {Ching Yu} and Kenji Yamashiro and {Jia Chen}, Li and Jeeyun Ahn and Lulin Huang and Lvzhen Huang and Cheung, {Chui Ming G.} and Masahiro Miyake and Cackett, {Peter D.} and Yeo, {Ian Y.} and Augustinus Laude and Ranjana Mathur and Junxiong Pang and Sim, {Kar Seng} and Koh, {Adrian H.} and Peng Chen and Lee, {Shu Yen} and Doric Wong and Chan, {Choi Mun} and Loh, {Boon Kwang} and Yaoyao Sun and Sonia Davila and Isao Nakata and Hideo Nakanishi and Yumiko Akagi-Kurashige and Norimoto Gotoh and Akitaka Tsujikawa and Fumihiko Matsuda and Keisuke Mori and Shin Yoneya and Yoichi Sakurada and Hiroyuki Iijima and Tomohiro Iida and Shigeru Honda and Lai, {Timothy Yuk Yau} and Tam, {Pancy Oi Sin} and Haoyu Chen and Shibo Tang and Xiaoyan Ding and Feng Wen and Fang Lu and Xiongze Zhang and Yi Shi and Peiquan Zhao and Bowen Zhao and Jinghong Sang and Bo Gong and Rajkumar Dorajoo and Yuan, {Jian Min} and Koh, {Woon Puay} and {Van Dam}, {Rob M.} and Yechiel Friedlander and Ying Lin and Hibberd, {Martin L.} and Foo, {Jia Nee} and Ningli Wang and Wong, {Chang Hua} and Tan, {Gavin S.} and Park, {Sang Jun} and Mayuri Bhargava and Lingam Gopal and Thet Naing and Jiemin Liao and {Guan Ong}, Peng and Paul Mitchell and Peng Zhou and Xuefeng Xie and Jinlong Liang and Junpu Mei and Xin Jin and Saw, {Seang Mei} and Mineo Ozaki and Takanori Mizoguchi and Yasuo Kurimoto and Woo, {Se Joon} and Hum Chung and Yu, {Hyeong Gon} and Shin, {Joo Young} and Park, {Dong Ho} and Kim, {In Taek} and Woohyok Chang and Min Sagong and Lee, {Sang Joon} and Kim, {Hyun Woong} and Lee, {Ji Eun} and Yi Li and Jianjun Liu and Teo, {Yik Ying} and Heng, {Chew Kiat} and Lim, {Tock Han} and Yang, {Suk Kyun} and Kyuyoung Song and Vithana, {Eranga N.} and Tin Aung and Bei, {Jin Xin} and Zeng, {Yi Xin} and Tai, {E. Shyong} and Li, {Xiao Xin} and Zhenglin Yang and Park, {Kyu Hyung} and Pang, {Chi Pui} and Nagahisa Yoshimura and {Yin Wong}, Tien and Khor, {Chiea Chuen}",

year = "2015",

month = jan,

day = "28",

doi = "10.1038/ncomms7063",

language = "English",

volume = "6",

journal = "Nature Communications",

issn = "2041-1723",

publisher = "Nature Publishing Group",

}

Cheng, CY, Yamashiro, K, Jia Chen, L, Ahn, J, Huang, L, Huang, L, Cheung, CMG, Miyake, M, Cackett, PD, Yeo, IY, Laude, A, Mathur, R, Pang, J, Sim, KS, Koh, AH, Chen, P, Lee, SY, Wong, D, Chan, CM, Loh, BK, Sun, Y, Davila, S, Nakata, I, Nakanishi, H, Akagi-Kurashige, Y, Gotoh, N, Tsujikawa, A, Matsuda, F, Mori, K, Yoneya, S, Sakurada, Y, Iijima, H, Iida, T, Honda, S, Lai, TYY, Tam, POS, Chen, H, Tang, S, Ding, X, Wen, F, Lu, F, Zhang, X, Shi, Y, Zhao, P, Zhao, B, Sang, J, Gong, B, Dorajoo, R, Yuan, JM, Koh, WP, Van Dam, RM, Friedlander, Y, Lin, Y, Hibberd, ML, Foo, JN, Wang, N, Wong, CH, Tan, GS, Park, SJ, Bhargava, M, Gopal, L, Naing, T, Liao, J, Guan Ong, P, Mitchell, P, Zhou, P, Xie, X, Liang, J, Mei, J, Jin, X, Saw, SM, Ozaki, M, Mizoguchi, T, Kurimoto, Y, Woo, SJ, Chung, H, Yu, HG, Shin, JY, Park, DH, Kim, IT, Chang, W, Sagong, M, Lee, SJ, Kim, HW, Lee, JE, Li, Y, Liu, J, Teo, YY, Heng, CK, Lim, TH, Yang, SK, Song, K, Vithana, EN, Aung, T, Bei, JX, Zeng, YX, Tai, ES, Li, XX, Yang, Z, Park, KH, Pang, CP, Yoshimura, N, Yin Wong, T & Khor, CC 2015, 'New loci and coding variants confer risk for age-related macular degeneration in East Asians', Nature Communications, vol. 6, 6063. https://doi.org/10.1038/ncomms7063

TY - JOUR

T1 - New loci and coding variants confer risk for age-related macular degeneration in East Asians

AU - Cheng, Ching Yu

AU - Yamashiro, Kenji

AU - Jia Chen, Li

AU - Ahn, Jeeyun

AU - Huang, Lulin

AU - Huang, Lvzhen

AU - Cheung, Chui Ming G.

AU - Miyake, Masahiro

AU - Cackett, Peter D.

AU - Yeo, Ian Y.

AU - Laude, Augustinus

AU - Mathur, Ranjana

AU - Pang, Junxiong

AU - Sim, Kar Seng

AU - Koh, Adrian H.

AU - Chen, Peng

AU - Lee, Shu Yen

AU - Wong, Doric

AU - Chan, Choi Mun

AU - Loh, Boon Kwang

AU - Sun, Yaoyao

AU - Davila, Sonia

AU - Nakata, Isao

AU - Nakanishi, Hideo

AU - Akagi-Kurashige, Yumiko

AU - Gotoh, Norimoto

AU - Tsujikawa, Akitaka

AU - Matsuda, Fumihiko

AU - Mori, Keisuke

AU - Yoneya, Shin

AU - Sakurada, Yoichi

AU - Iijima, Hiroyuki

AU - Iida, Tomohiro

AU - Honda, Shigeru

AU - Lai, Timothy Yuk Yau

AU - Tam, Pancy Oi Sin

AU - Chen, Haoyu

AU - Tang, Shibo

AU - Ding, Xiaoyan

AU - Wen, Feng

AU - Lu, Fang

AU - Zhang, Xiongze

AU - Shi, Yi

AU - Zhao, Peiquan

AU - Zhao, Bowen

AU - Sang, Jinghong

AU - Gong, Bo

AU - Dorajoo, Rajkumar

AU - Yuan, Jian Min

AU - Koh, Woon Puay

AU - Van Dam, Rob M.

AU - Friedlander, Yechiel

AU - Lin, Ying

AU - Hibberd, Martin L.

AU - Foo, Jia Nee

AU - Wang, Ningli

AU - Wong, Chang Hua

AU - Tan, Gavin S.

AU - Park, Sang Jun

AU - Bhargava, Mayuri

AU - Gopal, Lingam

AU - Naing, Thet

AU - Liao, Jiemin

AU - Guan Ong, Peng

AU - Mitchell, Paul

AU - Zhou, Peng

AU - Xie, Xuefeng

AU - Liang, Jinlong

AU - Mei, Junpu

AU - Jin, Xin

AU - Saw, Seang Mei

AU - Ozaki, Mineo

AU - Mizoguchi, Takanori

AU - Kurimoto, Yasuo

AU - Woo, Se Joon

AU - Chung, Hum

AU - Yu, Hyeong Gon

AU - Shin, Joo Young

AU - Park, Dong Ho

AU - Kim, In Taek

AU - Chang, Woohyok

AU - Sagong, Min

AU - Lee, Sang Joon

AU - Kim, Hyun Woong

AU - Lee, Ji Eun

AU - Li, Yi

AU - Liu, Jianjun

AU - Teo, Yik Ying

AU - Heng, Chew Kiat

AU - Lim, Tock Han

AU - Yang, Suk Kyun

AU - Song, Kyuyoung

AU - Vithana, Eranga N.

AU - Aung, Tin

AU - Bei, Jin Xin

AU - Zeng, Yi Xin

AU - Tai, E. Shyong

AU - Li, Xiao Xin

AU - Yang, Zhenglin

AU - Park, Kyu Hyung

AU - Pang, Chi Pui

AU - Yoshimura, Nagahisa

AU - Yin Wong, Tien

AU - Khor, Chiea Chuen

PY - 2015/1/28

Y1 - 2015/1/28

N2 - Age-related macular degeneration (AMD) is a major cause of blindness, but presents differently in Europeans and Asians. Here, we perform a genome-wide and exome-wide association study on 2,119 patients with exudative AMD and 5,691 controls, with independent replication in 4,226 patients and 10,289 controls, all of East Asian descent, as part of The Genetics of AMD in Asians (GAMA) Consortium. We find a strong association between CETP Asp442Gly (rs2303790), an East Asian-specific mutation, and increased risk of AMD (odds ratio (OR)=1.70, P=5.60 × 10-22). The AMD risk allele (442Gly), known to protect from coronary heart disease, increases HDL cholesterol levels by 0.17mmoll-1 (P=5.82 × 10-21) in East Asians (n=7,102). We also identify three novel AMD loci: C6orf223 Ala231Ala (OR=0.78, P=6.19 × 10-18), SLC44A4 Asp47Val (OR=1.27, P=1.08 × 10-11) and FGD6 Gln257Arg (OR=0.87, P=2.85 × 10-8). Our findings suggest that some of the genetic loci conferring AMD susceptibility in East Asians are shared with Europeans, yet AMD in East Asians may also have a distinct genetic signature.

AB - Age-related macular degeneration (AMD) is a major cause of blindness, but presents differently in Europeans and Asians. Here, we perform a genome-wide and exome-wide association study on 2,119 patients with exudative AMD and 5,691 controls, with independent replication in 4,226 patients and 10,289 controls, all of East Asian descent, as part of The Genetics of AMD in Asians (GAMA) Consortium. We find a strong association between CETP Asp442Gly (rs2303790), an East Asian-specific mutation, and increased risk of AMD (odds ratio (OR)=1.70, P=5.60 × 10-22). The AMD risk allele (442Gly), known to protect from coronary heart disease, increases HDL cholesterol levels by 0.17mmoll-1 (P=5.82 × 10-21) in East Asians (n=7,102). We also identify three novel AMD loci: C6orf223 Ala231Ala (OR=0.78, P=6.19 × 10-18), SLC44A4 Asp47Val (OR=1.27, P=1.08 × 10-11) and FGD6 Gln257Arg (OR=0.87, P=2.85 × 10-8). Our findings suggest that some of the genetic loci conferring AMD susceptibility in East Asians are shared with Europeans, yet AMD in East Asians may also have a distinct genetic signature.

UR - http://www.scopus.com/inward/record.url?scp=84955057955&partnerID=8YFLogxK

U2 - 10.1038/ncomms7063

DO - 10.1038/ncomms7063

M3 - Article

C2 - 25629512

AN - SCOPUS:84955057955

SN - 2041-1723

VL - 6

JO - Nature Communications

JF - Nature Communications

M1 - 6063

ER -

New loci and coding variants confer risk for age-related macular degeneration in East Asians

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