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