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

Journal Article (Journal Article)

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.

Full Text

Duke Authors

Cited Authors

  • Cheng, C-Y; Yamashiro, K; Chen, LJ; 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, J-M; Koh, W-P; 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; Ong, PG; Mitchell, P; Zhou, P; Xie, X; Liang, J; Mei, J; Jin, X; Saw, S-M; Ozaki, M; Mizoguchi, T; Kurimoto, Y; Woo, SJ; Chung, H; Yu, H-G; Shin, JY; Park, DH; Kim, IT; Chang, W; Sagong, M; Lee, S-J; Kim, HW; Lee, JE; Li, Y; Liu, J; Teo, YY; Heng, CK; Lim, TH; Yang, S-K; Song, K; Vithana, EN; Aung, T; Bei, JX; Zeng, YX; Tai, ES; Li, XX; Yang, Z; Park, K-H; Pang, CP; Yoshimura, N; Wong, TY; Khor, CC

Published Date

  • January 28, 2015

Published In

Volume / Issue

  • 6 /

Start / End Page

  • 6063 -

PubMed ID

  • 25629512

Pubmed Central ID

  • PMC4317498

Electronic International Standard Serial Number (EISSN)

  • 2041-1723

Digital Object Identifier (DOI)

  • 10.1038/ncomms7063


  • eng

Conference Location

  • England