A genome-wide association study identified a novel genetic loci STON1-GTF2A1L/LHCGR/FSHR for bilaterality of neovascular age-related macular degeneration
Abstract 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 ha...
Main Authors: | , , , , , , , , , , , , , , , , , , , , , , , , |
---|---|
Format: | Article |
Language: | English |
Published: |
Nature Publishing Group
2017-08-01
|
Series: | Scientific Reports |
Online Access: | https://doi.org/10.1038/s41598-017-07526-9 |
id |
doaj-51f45ede27f14284a3b7850c22ea583a |
---|---|
record_format |
Article |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Kyoko Kawashima-Kumagai Kenji Yamashiro Munemitsu Yoshikawa Masahiro Miyake Gemmy Cheung Chui Ming Qiao Fan Jia Yu Koh Masaaki Saito Masako Sugahara-Kuroda Maho Oishi Yumiko Akagi-Kurashige Isao Nakata Hideo Nakanishi Norimoto Gotoh Akio Oishi Hiroshi Tamura Sotaro Ooto Akitaka Tsujikawa Yasuo Kurimoto Tetsuju Sekiryu Fumihiko Matsuda Chiea-Chuen Khor Ching-Yu Cheng Tien Yin Wong Nagahisa Yoshimura |
spellingShingle |
Kyoko Kawashima-Kumagai Kenji Yamashiro Munemitsu Yoshikawa Masahiro Miyake Gemmy Cheung Chui Ming Qiao Fan Jia Yu Koh Masaaki Saito Masako Sugahara-Kuroda Maho Oishi Yumiko Akagi-Kurashige Isao Nakata Hideo Nakanishi Norimoto Gotoh Akio Oishi Hiroshi Tamura Sotaro Ooto Akitaka Tsujikawa Yasuo Kurimoto Tetsuju Sekiryu Fumihiko Matsuda Chiea-Chuen Khor Ching-Yu Cheng Tien Yin Wong Nagahisa Yoshimura A genome-wide association study identified a novel genetic loci STON1-GTF2A1L/LHCGR/FSHR for bilaterality of neovascular age-related macular degeneration Scientific Reports |
author_facet |
Kyoko Kawashima-Kumagai Kenji Yamashiro Munemitsu Yoshikawa Masahiro Miyake Gemmy Cheung Chui Ming Qiao Fan Jia Yu Koh Masaaki Saito Masako Sugahara-Kuroda Maho Oishi Yumiko Akagi-Kurashige Isao Nakata Hideo Nakanishi Norimoto Gotoh Akio Oishi Hiroshi Tamura Sotaro Ooto Akitaka Tsujikawa Yasuo Kurimoto Tetsuju Sekiryu Fumihiko Matsuda Chiea-Chuen Khor Ching-Yu Cheng Tien Yin Wong Nagahisa Yoshimura |
author_sort |
Kyoko Kawashima-Kumagai |
title |
A genome-wide association study identified a novel genetic loci STON1-GTF2A1L/LHCGR/FSHR for bilaterality of neovascular age-related macular degeneration |
title_short |
A genome-wide association study identified a novel genetic loci STON1-GTF2A1L/LHCGR/FSHR for bilaterality of neovascular age-related macular degeneration |
title_full |
A genome-wide association study identified a novel genetic loci STON1-GTF2A1L/LHCGR/FSHR for bilaterality of neovascular age-related macular degeneration |
title_fullStr |
A genome-wide association study identified a novel genetic loci STON1-GTF2A1L/LHCGR/FSHR for bilaterality of neovascular age-related macular degeneration |
title_full_unstemmed |
A genome-wide association study identified a novel genetic loci STON1-GTF2A1L/LHCGR/FSHR for bilaterality of neovascular age-related macular degeneration |
title_sort |
genome-wide association study identified a novel genetic loci ston1-gtf2a1l/lhcgr/fshr for bilaterality of neovascular age-related macular degeneration |
publisher |
Nature Publishing Group |
series |
Scientific Reports |
issn |
2045-2322 |
publishDate |
2017-08-01 |
description |
Abstract 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. |
url |
https://doi.org/10.1038/s41598-017-07526-9 |
work_keys_str_mv |
AT kyokokawashimakumagai agenomewideassociationstudyidentifiedanovelgeneticlociston1gtf2a1llhcgrfshrforbilateralityofneovascularagerelatedmaculardegeneration AT kenjiyamashiro agenomewideassociationstudyidentifiedanovelgeneticlociston1gtf2a1llhcgrfshrforbilateralityofneovascularagerelatedmaculardegeneration AT munemitsuyoshikawa agenomewideassociationstudyidentifiedanovelgeneticlociston1gtf2a1llhcgrfshrforbilateralityofneovascularagerelatedmaculardegeneration AT masahiromiyake agenomewideassociationstudyidentifiedanovelgeneticlociston1gtf2a1llhcgrfshrforbilateralityofneovascularagerelatedmaculardegeneration AT gemmycheungchuiming agenomewideassociationstudyidentifiedanovelgeneticlociston1gtf2a1llhcgrfshrforbilateralityofneovascularagerelatedmaculardegeneration AT qiaofan agenomewideassociationstudyidentifiedanovelgeneticlociston1gtf2a1llhcgrfshrforbilateralityofneovascularagerelatedmaculardegeneration AT jiayukoh agenomewideassociationstudyidentifiedanovelgeneticlociston1gtf2a1llhcgrfshrforbilateralityofneovascularagerelatedmaculardegeneration AT masaakisaito agenomewideassociationstudyidentifiedanovelgeneticlociston1gtf2a1llhcgrfshrforbilateralityofneovascularagerelatedmaculardegeneration AT masakosugaharakuroda agenomewideassociationstudyidentifiedanovelgeneticlociston1gtf2a1llhcgrfshrforbilateralityofneovascularagerelatedmaculardegeneration AT mahooishi agenomewideassociationstudyidentifiedanovelgeneticlociston1gtf2a1llhcgrfshrforbilateralityofneovascularagerelatedmaculardegeneration AT yumikoakagikurashige agenomewideassociationstudyidentifiedanovelgeneticlociston1gtf2a1llhcgrfshrforbilateralityofneovascularagerelatedmaculardegeneration AT isaonakata agenomewideassociationstudyidentifiedanovelgeneticlociston1gtf2a1llhcgrfshrforbilateralityofneovascularagerelatedmaculardegeneration AT hideonakanishi agenomewideassociationstudyidentifiedanovelgeneticlociston1gtf2a1llhcgrfshrforbilateralityofneovascularagerelatedmaculardegeneration AT norimotogotoh agenomewideassociationstudyidentifiedanovelgeneticlociston1gtf2a1llhcgrfshrforbilateralityofneovascularagerelatedmaculardegeneration AT akiooishi agenomewideassociationstudyidentifiedanovelgeneticlociston1gtf2a1llhcgrfshrforbilateralityofneovascularagerelatedmaculardegeneration AT hiroshitamura agenomewideassociationstudyidentifiedanovelgeneticlociston1gtf2a1llhcgrfshrforbilateralityofneovascularagerelatedmaculardegeneration AT sotaroooto agenomewideassociationstudyidentifiedanovelgeneticlociston1gtf2a1llhcgrfshrforbilateralityofneovascularagerelatedmaculardegeneration AT akitakatsujikawa agenomewideassociationstudyidentifiedanovelgeneticlociston1gtf2a1llhcgrfshrforbilateralityofneovascularagerelatedmaculardegeneration AT yasuokurimoto agenomewideassociationstudyidentifiedanovelgeneticlociston1gtf2a1llhcgrfshrforbilateralityofneovascularagerelatedmaculardegeneration AT tetsujusekiryu agenomewideassociationstudyidentifiedanovelgeneticlociston1gtf2a1llhcgrfshrforbilateralityofneovascularagerelatedmaculardegeneration AT fumihikomatsuda agenomewideassociationstudyidentifiedanovelgeneticlociston1gtf2a1llhcgrfshrforbilateralityofneovascularagerelatedmaculardegeneration AT chieachuenkhor agenomewideassociationstudyidentifiedanovelgeneticlociston1gtf2a1llhcgrfshrforbilateralityofneovascularagerelatedmaculardegeneration AT chingyucheng agenomewideassociationstudyidentifiedanovelgeneticlociston1gtf2a1llhcgrfshrforbilateralityofneovascularagerelatedmaculardegeneration AT tienyinwong agenomewideassociationstudyidentifiedanovelgeneticlociston1gtf2a1llhcgrfshrforbilateralityofneovascularagerelatedmaculardegeneration AT nagahisayoshimura agenomewideassociationstudyidentifiedanovelgeneticlociston1gtf2a1llhcgrfshrforbilateralityofneovascularagerelatedmaculardegeneration AT kyokokawashimakumagai genomewideassociationstudyidentifiedanovelgeneticlociston1gtf2a1llhcgrfshrforbilateralityofneovascularagerelatedmaculardegeneration AT kenjiyamashiro genomewideassociationstudyidentifiedanovelgeneticlociston1gtf2a1llhcgrfshrforbilateralityofneovascularagerelatedmaculardegeneration AT munemitsuyoshikawa genomewideassociationstudyidentifiedanovelgeneticlociston1gtf2a1llhcgrfshrforbilateralityofneovascularagerelatedmaculardegeneration AT masahiromiyake genomewideassociationstudyidentifiedanovelgeneticlociston1gtf2a1llhcgrfshrforbilateralityofneovascularagerelatedmaculardegeneration AT gemmycheungchuiming genomewideassociationstudyidentifiedanovelgeneticlociston1gtf2a1llhcgrfshrforbilateralityofneovascularagerelatedmaculardegeneration AT qiaofan genomewideassociationstudyidentifiedanovelgeneticlociston1gtf2a1llhcgrfshrforbilateralityofneovascularagerelatedmaculardegeneration AT jiayukoh genomewideassociationstudyidentifiedanovelgeneticlociston1gtf2a1llhcgrfshrforbilateralityofneovascularagerelatedmaculardegeneration AT masaakisaito genomewideassociationstudyidentifiedanovelgeneticlociston1gtf2a1llhcgrfshrforbilateralityofneovascularagerelatedmaculardegeneration AT masakosugaharakuroda genomewideassociationstudyidentifiedanovelgeneticlociston1gtf2a1llhcgrfshrforbilateralityofneovascularagerelatedmaculardegeneration AT mahooishi genomewideassociationstudyidentifiedanovelgeneticlociston1gtf2a1llhcgrfshrforbilateralityofneovascularagerelatedmaculardegeneration AT yumikoakagikurashige genomewideassociationstudyidentifiedanovelgeneticlociston1gtf2a1llhcgrfshrforbilateralityofneovascularagerelatedmaculardegeneration AT isaonakata genomewideassociationstudyidentifiedanovelgeneticlociston1gtf2a1llhcgrfshrforbilateralityofneovascularagerelatedmaculardegeneration AT hideonakanishi genomewideassociationstudyidentifiedanovelgeneticlociston1gtf2a1llhcgrfshrforbilateralityofneovascularagerelatedmaculardegeneration AT norimotogotoh genomewideassociationstudyidentifiedanovelgeneticlociston1gtf2a1llhcgrfshrforbilateralityofneovascularagerelatedmaculardegeneration AT akiooishi genomewideassociationstudyidentifiedanovelgeneticlociston1gtf2a1llhcgrfshrforbilateralityofneovascularagerelatedmaculardegeneration AT hiroshitamura genomewideassociationstudyidentifiedanovelgeneticlociston1gtf2a1llhcgrfshrforbilateralityofneovascularagerelatedmaculardegeneration AT sotaroooto genomewideassociationstudyidentifiedanovelgeneticlociston1gtf2a1llhcgrfshrforbilateralityofneovascularagerelatedmaculardegeneration AT akitakatsujikawa genomewideassociationstudyidentifiedanovelgeneticlociston1gtf2a1llhcgrfshrforbilateralityofneovascularagerelatedmaculardegeneration AT yasuokurimoto genomewideassociationstudyidentifiedanovelgeneticlociston1gtf2a1llhcgrfshrforbilateralityofneovascularagerelatedmaculardegeneration AT tetsujusekiryu genomewideassociationstudyidentifiedanovelgeneticlociston1gtf2a1llhcgrfshrforbilateralityofneovascularagerelatedmaculardegeneration AT fumihikomatsuda genomewideassociationstudyidentifiedanovelgeneticlociston1gtf2a1llhcgrfshrforbilateralityofneovascularagerelatedmaculardegeneration AT chieachuenkhor genomewideassociationstudyidentifiedanovelgeneticlociston1gtf2a1llhcgrfshrforbilateralityofneovascularagerelatedmaculardegeneration AT chingyucheng genomewideassociationstudyidentifiedanovelgeneticlociston1gtf2a1llhcgrfshrforbilateralityofneovascularagerelatedmaculardegeneration AT tienyinwong genomewideassociationstudyidentifiedanovelgeneticlociston1gtf2a1llhcgrfshrforbilateralityofneovascularagerelatedmaculardegeneration AT nagahisayoshimura genomewideassociationstudyidentifiedanovelgeneticlociston1gtf2a1llhcgrfshrforbilateralityofneovascularagerelatedmaculardegeneration |
_version_ |
1724394649235226624 |
spelling |
doaj-51f45ede27f14284a3b7850c22ea583a2020-12-08T01:36:43ZengNature Publishing GroupScientific Reports2045-23222017-08-01711810.1038/s41598-017-07526-9A genome-wide association study identified a novel genetic loci STON1-GTF2A1L/LHCGR/FSHR for bilaterality of neovascular age-related macular degenerationKyoko Kawashima-Kumagai0Kenji Yamashiro1Munemitsu Yoshikawa2Masahiro Miyake3Gemmy Cheung Chui Ming4Qiao Fan5Jia Yu Koh6Masaaki Saito7Masako Sugahara-Kuroda8Maho Oishi9Yumiko Akagi-Kurashige10Isao Nakata11Hideo Nakanishi12Norimoto Gotoh13Akio Oishi14Hiroshi Tamura15Sotaro Ooto16Akitaka Tsujikawa17Yasuo Kurimoto18Tetsuju Sekiryu19Fumihiko Matsuda20Chiea-Chuen Khor21Ching-Yu Cheng22Tien Yin Wong23Nagahisa Yoshimura24Department of Ophthalmology and Visual Sciences, Kyoto University Graduate School of MedicineDepartment of Ophthalmology and Visual Sciences, Kyoto University Graduate School of MedicineDepartment of Ophthalmology and Visual Sciences, Kyoto University Graduate School of MedicineDepartment of Ophthalmology and Visual Sciences, Kyoto University Graduate School of MedicineSingapore Eye Research Institute, Singapore National Eye CentreSingapore Eye Research Institute, Singapore National Eye CentreSingapore Eye Research Institute, Singapore National Eye CentreDepartment of Ophthalmology, Fukushima Medical UniversityDepartment of Ophthalmology and Visual Sciences, Kyoto University Graduate School of MedicineDepartment of Ophthalmology and Visual Sciences, Kyoto University Graduate School of MedicineDepartment of Ophthalmology and Visual Sciences, Kyoto University Graduate School of MedicineDepartment of Ophthalmology and Visual Sciences, Kyoto University Graduate School of MedicineDepartment of Ophthalmology and Visual Sciences, Kyoto University Graduate School of MedicineCenter for Genomic Medicine, Kyoto University Graduate School of MedicineDepartment of Ophthalmology and Visual Sciences, Kyoto University Graduate School of MedicineDepartment of Ophthalmology and Visual Sciences, Kyoto University Graduate School of MedicineDepartment of Ophthalmology and Visual Sciences, Kyoto University Graduate School of MedicineDepartment of Ophthalmology and Visual Sciences, Kyoto University Graduate School of MedicineDepartment of Ophthalmology, Kobe City General HospitalDepartment of Ophthalmology, Fukushima Medical UniversityCenter for Genomic Medicine, Kyoto University Graduate School of MedicineSingapore Eye Research Institute, Singapore National Eye CentreSingapore Eye Research Institute, Singapore National Eye CentreSingapore Eye Research Institute, Singapore National Eye CentreDepartment of Ophthalmology and Visual Sciences, Kyoto University Graduate School of MedicineAbstract 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.https://doi.org/10.1038/s41598-017-07526-9 |