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

Kawashima-Kumagai K, Yamashiro K, Yoshikawa M et al.

28775256 PubMed ID
GWAS Study Type
1394 Participants
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Chapter I

Publication Details

Comprehensive information about this research publication

Authors

KK
Kawashima-Kumagai K
YK
Yamashiro K
YM
Yoshikawa M
MM
Miyake M
MG
Ming GCC
FQ
Fan Q
KJ
Koh JY
SM
Saito M
SM
Sugahara-Kuroda M
OM
Oishi M
AY
Akagi-Kurashige Y
NI
Nakata I
NH
Nakanishi H
GN
Gotoh N
OA
Oishi A
TH
Tamura H
OS
Ooto S
TA
Tsujikawa A
KY
Kurimoto Y
ST
Sekiryu T
MF
Matsuda F
KC
Khor CC
CC
Cheng CY
WT
Wong TY
YN
Yoshimura N
Chapter II

Abstract

Summary of the research findings

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.

803 Japanese ancestry unilateral cases, 321 Japanese ancestry bilateral cases

Chapter III

Study Statistics

Key metrics and study information

1394
Total Participants
GWAS
Study Type
Yes
Replicated
132 Japanese ancestry unilateral cases, 36 Japanese ancestry bilateral cases, 78 Asian ancestry unilateral cases, 24 Asian ancestry bilateral cases
Replication Participants
Asian unspecified, East Asian
Ancestry
Singapore, Japan
Recruitment Country
Chapter IV

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