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 0.17 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.

• Authors: 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
• Journal: Nature communications (Nat Commun) Vol. 6 Pg. 6063 (Jan 28 2015) ISSN: 2041-1723 [Electronic] England
• PMID: 25629512 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

• CETP protein, human
• Cholesterol Ester Transfer Proteins
• Cholesterol, HDL

Topics

• Asian People (genetics)
• Case-Control Studies
• Cholesterol Ester Transfer Proteins (genetics)
• Cholesterol, HDL (blood)
• Cohort Studies
• Coronary Disease (blood, genetics)
• Exome (genetics)
• Genetic Loci
• Genetic Predisposition to Disease
• Genome-Wide Association Study
• Humans
• Macular Degeneration (blood, genetics)
• Mutation (genetics)
• Polymorphism, Single Nucleotide (genetics)
• Reproducibility of Results
• Risk Factors