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

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 c...

Descripción completa

Detalles Bibliográficos
Autores principales: 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
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Pub. Group 2015
Materias:
Article
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4317498/
https://www.ncbi.nlm.nih.gov/pubmed/25629512
http://dx.doi.org/10.1038/ncomms7063
Descripción
Sumario: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.

Ejemplares similares