Ching-Yu Cheng^1,2,3,4,*, Kenji Yamashiro^5,*, Li Jia Chen^6,*, Jeeyun Ahn^7,*, Lulin Huang^8,9,*, Lvzhen Huang^10,11,12,*, Chui Ming G. Cheung^1,4, Masahiro Miyake^5,13, Peter D. Cackett^4,14, Ian Y. Yeo⁴, Augustinus Laude^1,15, Ranjana Mathur⁴, Junxiong Pang¹⁶, Kar Seng Sim¹⁶, Adrian H. Koh^4,17, Peng Chen¹⁸, Shu Yen Lee⁴, Doric Wong⁴, Choi Mun Chan⁴, Boon Kwang Loh⁴, Yaoyao Sun^10,11,12, Sonia Davila^3,16, Isao Nakata^5,13, Hideo Nakanishi⁵, Yumiko Akagi-Kurashige^5,13, Norimoto Gotoh⁵, Akitaka Tsujikawa⁵, Fumihiko Matsuda¹³, Keisuke Mori¹⁹, Shin Yoneya¹⁹, Yoichi Sakurada²⁰, Hiroyuki Iijima²⁰, Tomohiro Iida²¹, Shigeru Honda²², Timothy Yuk Yau Lai⁶, Pancy Oi Sin Tam⁶, Haoyu Chen^6,23, Shibo Tang^24,25, Xiaoyan Ding²⁴, Feng Wen²⁴, Fang Lu^8,9, Xiongze Zhang²⁴, Yi Shi^8,9, Peiquan Zhao²⁶, Bowen Zhao²⁷, Jinghong Sang²⁷, Bo Gong^8,9, Rajkumar Dorajoo¹⁶, Jian-Min Yuan^28,29, Woon-Puay Koh^2,18, Rob M. van Dam¹⁸, Yechiel Friedlander³⁰, Ying Lin^8,9, Martin L. Hibberd¹⁶, Jia Nee Foo¹⁶, Ningli Wang²⁷, Chang Hua Wong¹⁶, Gavin S. Tan⁴, Sang Jun Park³¹, Mayuri Bhargava^1,3, Lingam Gopal³, Thet Naing³, Jiemin Liao^1,3, Peng Guan Ong¹, Paul Mitchell³², Peng Zhou³³, Xuefeng Xie³⁴, Jinlong Liang³⁴, Junpu Mei³⁴, Xin Jin³⁴, Seang-Mei Saw^1,2,3,18, Mineo Ozaki³⁵, Takanori Mizoguchi³⁶, Yasuo Kurimoto³⁷, Se Joon Woo^31,38, Hum Chung³⁸, Hyeong-Gon Yu³⁸, Joo Young Shin³⁸, Dong Ho Park³⁹, In Taek Kim³⁹, Woohyok Chang⁴⁰, Min Sagong⁴⁰, Sang-Joon Lee⁴¹, Hyun Woong Kim⁴², Ji Eun Lee^43,44, Yi Li¹⁶, Jianjun Liu^16,18, Yik Ying Teo^16,18, Chew Kiat Heng⁴⁵, Tock Han Lim¹⁵, Suk-Kyun Yang⁴⁶, Kyuyoung Song⁴⁷, Eranga N. Vithana^1,2,3, Tin Aung^1,3,4, Jin Xin Bei^48,49, Yi Xin Zeng^48,49,50, E. Shyong Tai^2,18,51,§, Xiao Xin Li^10,11,12,§, Zhenglin Yang^8,9,§, Kyu-Hyung Park^31,§, Chi Pui Pang^6,§, Nagahisa Yoshimura^5,§, Tien Yin Wong^1,2,3,4 & Chiea Chuen Khor^1,16,18

¹ Singapore Eye Research Institute, Singapore 169856, Singapore. ² Duke-NUS Graduate Medical School, National University of Singapore, Singapore 169857, Singapore. ³ Department of Ophthalmology, National University of Singapore and National University Health System, Singapore 119228, Singapore. ⁴ Singapore National Eye Center, Singapore 168751, Singapore. ⁵ Department of Ophthalmology and Visual Sciences, Kyoto University Graduate School of Medicine, Kyoto 6068507, Japan. ⁶ Department of Ophthalmology and Visual Sciences, The Chinese University of Hong Kong, Hong Kong, China. ⁷ Department of Ophthalmology, Seoul Metropolitan Government Seoul National University Boramae Medical Center, Seoul 156-707, Korea. ⁸ Sichuan Provincial Key Laboratory for Human Disease Gene Study, Hospital of the University of Electronic Science and Technology of China and Sichuan Provincial People’s Hospital, Chengdu 610072, China. ⁹ School of Medicine, University of Electronic Science and Technology of China, Chengdu 610072, China. ¹⁰ Key Laboratory of Vision Loss and Restoration, Ministry of Education of China, Beijing 100044, China. ¹¹ Beijing Key Laboratory of Diagnosis and Therapy of Retinal and Choroid Diseases, Beijing 100871, China. ¹² Department of Ophthalmology, People’s Hospital, Peking University, Beijing 100871, China. ¹³ Center for Genomic Medicine/Inserm U.852, Kyoto University Graduate School of Medicine, Kyoto 6068507, Japan. ¹⁴ Princess Alexandra Eye Pavilion, Edinburgh EH3 9HA, UK. ¹⁵ National Healthcare Group Eye Institute, Tan Tock Seng Hospital, Singapore 308433, Singapore. ¹⁶ Division of Human Genetics, Genome Institute of Singapore, Singapore 138672, Singapore. ¹⁷ Eye and Retinal Surgeons, Camden Medical Centre, Singapore 248649, Singapore. ¹⁸ Saw Swee Hock School of Public Health, National University of Singapore and National University Health System, Singapore 117549, Singapore. ¹⁹ Department of Ophthalmology, Saitama Medical University, Iruma 3500495, Japan. ²⁰ Department of Ophthalmology, Faculty of Medicine, University of Yamanashi, Yamanashi 4093898, Japan. ²¹ Department of Ophthalmology, TokyoWomen’s Medical University Hospital, Tokyo 1628666, Japan. ²² Department of Surgery, Division of Ophthalmology, Kobe University Graduate School of Medicine, Kobe 6500017, Japan. ²³ Shantou University/Chinese University of Hong Kong Joint Shantou International Eye Center, Shantou 515041, China. ²⁴ Zhongshan Ophthalmic Center, Sun Yat-Sen University, Guangzhou 510060, China. ²⁵ Aier School of Ophthalmology, Central South University, Changsha 410000, China. ²⁶ Department of Ophthalmology, Xin Hua Hospital affiliated to Shanghai Jiao Tong University, School of Medicine, Shanghai 200025, China. ²⁷ Beijing Tongren Eye Center, Beijing Tongren Hospital, Capital Medical University, Beijing Institute of Ophthalmology, Beijing 100730, China. ²⁸ Cancer Control and Population Sciences, University of Pittsburgh Cancer Institute, Pittsburgh, Pennsylvania 15260, USA. ²⁹ Department of Epidemiology, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, Pennsylvania 15260, USA. ³⁰ Hebrew University, School of Public Health, Jerusalem 91120, Israel. ³¹ Department of Ophthalmology, Seoul National University Bundang Hospital, Gyeonggi 463-707, Korea. ³² Department of Ophthalmology, University of Sydney and Westmead Millennium Institute, Sydney 2145, Australia. ³³ Eye and ENT Hospital of Fudan University, Shanghai 200433, China. ³⁴ BGI-Shenzhen, Shenzhen 518083, China. ³⁵ Ozaki Eye Hospital, Miyazaki 8830066, Japan. ³⁶ Mizoguchi Eye Hospital, Nagasaki 8570016, Japan. ³⁷ Department of Ophthalmology, Kobe City General Hospital, Kobe 6500046, Japan. ³⁸ Department of Ophthalmology, Seoul National University Hospital, Seoul National University College of Medicine, Seoul 110-744, Korea. ³⁹ Department of Ophthalmology, School of Medicine, Kyungpook National University, Daegu 700-721, Korea. ⁴⁰ Department of Ophthalmology, Yeungnam University College of Medicine, Daegu 705-802, Korea. ⁴¹ Department of Ophthalmology, College of Medicine, Kosin University, Pusan 606-701, Korea. ⁴² Department of Ophthalmology, Pusan Paik Hospital, Inje University College of Medicine, Pusan 614-735, Korea. ⁴³ Department of Ophthalmology, Pusan National University Hospital, Pusan 602-739, Korea. ⁴⁴ Medical Research Institute, Pusan National University, Pusan 602-739, Korea. ⁴⁵ Department of Pediatrics, National University Health System and National University of Singapore, Singapore 119228, Singapore. ⁴⁶ Department of Gastroenterology, Asan Medical Center and University of Ulsan College of Medicine, Seoul 138-736, Korea. ⁴⁷ Department of Biochemistry and Molecular Biology, University of Ulsan College of Medicine, Seoul 138-736, Korea. ⁴⁸ State Key Laboratory of Oncology in Southern China, Guangzhou 510060, China. ⁴⁹ Department of Experimental Research, Sun Yat-Sen University Cancer Center, Guangzhou 510080, China. ⁵⁰ Peking Union Medical College, Chinese Academy of Medical Science, Beijing 100730, China. ⁵¹ Department of Medicine, National University Health System and National University of Singapore, Singapore 119228, Singapore.
^* These authors contributed equally to this work. y These authors jointly supervised this work.

Correspondence to: Ching-Yu Cheng or Tien Yin Wong or Chiea Chuen Khor

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 mmoll^-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.