A genome-wide association study identified a novel genetic loci STON1-GTF2A1L/LHCGR/FSHR for bilaterality of neovascular age-related macular degeneration.

Journal Article (Journal Article)

Bilateral neovascular age-related macular degeneration (AMD) causes much more handicaps for patients than unilateral neovascular AMD. Although several AMD-susceptibility genes have been evaluated for their associations to bilaterality, genome-wide association study (GWAS) on bilaterality has been rarely reported. In the present study, we performed GWAS using neovascular AMD cases in East Asian. The discovery stage compared 581,252 single nucleotide polymorphisms (SNPs) between 803 unilateral and 321 bilateral Japanese cases but no SNP showed genome-wide significance, while SNPs at six regions showed P-value < 1.0 × 10-5, STON1-GTF2A1L/LHCGR/FSHR, PLXNA1, CTNNA3, ARMS2/HTRA1, LHFP, and FLJ38725. The first replication study for these six regions comparing 36 bilateral and 132 unilateral Japanese cases confirmed significant associations of rs4482537 (STON1-GTF2A1L/LHCGR/FSHR), rs2284665 (ARMS2/HTRA1), and rs8002574 (LHFP) to bilaterality. In the second replication study comparing 24 bilateral and 78 unilateral cases from Singapore, rs4482537 (STON1-GTF2A1L/LHCGR/FSHR) only showed significant association. Meta-analysis of discovery and replication studies confirmed genome-wide level significant association (P = 2.61 × 10-9) of rs4482537 (STON1-GTF2A1L/LHCGR/FSHR) and strong associations (P = 5.76 × 10-7 and 9.73 × 10-7, respectively) of rs2284665 (ARMS2/HTRA1) and rs8002574 (LHFP). Our GWAS for neovascular AMD bilaterality found new genetic loci STON1-GTF2A1L/LHCGR/FSHR and confirmed the previously reported association of ARMS2/HTRA1.

Full Text

Duke Authors

Cited Authors

  • Kawashima-Kumagai, K; Yamashiro, K; Yoshikawa, M; Miyake, M; Ming, GCC; Fan, Q; Koh, JY; Saito, M; Sugahara-Kuroda, M; Oishi, M; Akagi-Kurashige, Y; Nakata, I; Nakanishi, H; Gotoh, N; Oishi, A; Tamura, H; Ooto, S; Tsujikawa, A; Kurimoto, Y; Sekiryu, T; Matsuda, F; Khor, C-C; Cheng, C-Y; Wong, TY; Yoshimura, N

Published Date

  • August 3, 2017

Published In

Volume / Issue

  • 7 / 1

Start / End Page

  • 7173 -

PubMed ID

  • 28775256

Pubmed Central ID

  • PMC5543064

Electronic International Standard Serial Number (EISSN)

  • 2045-2322

Digital Object Identifier (DOI)

  • 10.1038/s41598-017-07526-9


  • eng

Conference Location

  • England