TY - JOUR
T1 - Genome-wide meta-analysis identifies 22 loci for normal tension glaucoma with significant overlap with high tension glaucoma
AU - Diaz-Torres, Santiago
AU - He, Weixiong
AU - Yu, Regina
AU - IGGC International Glaucoma Genetics Consortium
AU - Khawaja, Anthony P
AU - Hammond, Christopher J
AU - Hysi, Pirro G
AU - Pasquale, Louis R
AU - Wu, Yeda
AU - Kubo, Michiaki
AU - Akiyama, Masato
AU - Aung, Tin
AU - Cheng, Ching-Yu
AU - Khor, Chiea Chuen
AU - Kraft, Peter
AU - Kang, Jae H
AU - Hewitt, Alex W
AU - Mackey, David A
AU - Craig, Jamie E
AU - Wiggs, Janey L
AU - Ong, Jue-Sheng
AU - MacGregor, Stuart
AU - Gharahkhani, Puya
AU - Han, Xikun
AU - Hamel, Andrew R
AU - Young, Terri L
AU - Lotery, Andrew J
AU - Jorgenson, Eric
AU - Choquet, Hélène
AU - Hauser, Michael
AU - Cooke Bailey, Jessica N
AU - Nakazawa, Toru
AU - Shiga, Yukihiro
AU - Segrè, Ayellet V
PY - 2024/11/17
Y1 - 2024/11/17
N2 - Primary open-angle glaucoma typically presents as two subtypes. This study aimed to elucidate the shared and distinct genetic architectures of normal-tension (NTG) and high-tension glaucoma (HTG), motivated by the need to develop intraocular pressure (IOP)-independent drug targets for the disease. We conducted a comprehensive multi-ethnic meta-analysis, prioritized variants based on functional annotation, and explored drug-gene interactions. We further assessed the genetic overlap between NTG and HTG using pairwise GWAS analysis. We identified 22 risk loci associated with NTG, 17 of which have not previously been reported for NTG. Two loci, BMP4 and TBKBP1, have not previously been associated with glaucoma at the genome-wide significance level. Our results indicate that while there is a significant overlap in risk loci between tension subtypes, the magnitude of the effect tends to be lower in NTG compared to HTG, particularly for IOP-related loci. Additionally, we identified a potential role for biologic immunomodulatory treatments as neuroprotective agents.
AB - Primary open-angle glaucoma typically presents as two subtypes. This study aimed to elucidate the shared and distinct genetic architectures of normal-tension (NTG) and high-tension glaucoma (HTG), motivated by the need to develop intraocular pressure (IOP)-independent drug targets for the disease. We conducted a comprehensive multi-ethnic meta-analysis, prioritized variants based on functional annotation, and explored drug-gene interactions. We further assessed the genetic overlap between NTG and HTG using pairwise GWAS analysis. We identified 22 risk loci associated with NTG, 17 of which have not previously been reported for NTG. Two loci, BMP4 and TBKBP1, have not previously been associated with glaucoma at the genome-wide significance level. Our results indicate that while there is a significant overlap in risk loci between tension subtypes, the magnitude of the effect tends to be lower in NTG compared to HTG, particularly for IOP-related loci. Additionally, we identified a potential role for biologic immunomodulatory treatments as neuroprotective agents.
KW - High-tension glaucoma
KW - Eye treatment
KW - Normal-tension glaucoma
KW - Open-angle glaucoma
UR - http://www.scopus.com/inward/record.url?scp=85209955368&partnerID=8YFLogxK
U2 - 10.1038/s41467-024-54301-2
DO - 10.1038/s41467-024-54301-2
M3 - Article
C2 - 39551815
AN - SCOPUS:85209955368
SN - 2041-1723
VL - 15
JO - Nature Communications
JF - Nature Communications
M1 - 9959
ER -