| Title: | Genome-wide meta-analysis identifies 22 loci for normal tension glaucoma with significant overlap with high tension glaucoma |
| Journal: | Nature Communications |
| Published: | 17 Nov 2024 |
| Pubmed: | https://pubmed.ncbi.nlm.nih.gov/39551815/ |
| DOI: | https://doi.org/10.1038/s41467-024-54301-2 |
Publication 14108
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Abstract
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.</p>
11 Keywords
- Bone Morphogenetic Protein 4
- Female
- Genetic Loci
- Genetic Predisposition to Disease
- Genome-Wide Association Study
- Glaucoma, Open-Angle
- Humans
- Intraocular Pressure
- Latent TGF-beta Binding Proteins
- Low Tension Glaucoma
- Polymorphism, Single Nucleotide
22 Authors
- Santiago Diaz-Torres
- Weixiong He
- Regina Yu
- Anthony P. Khawaja
- Christopher J. Hammond
- Pirro G. Hysi
- Louis R. Pasquale
- Yeda Wu
- Michiaki Kubo
- Masato Akiyama
- Tin Aung
- Ching-Yu Cheng
- Chiea Chuen Khor
- Peter Kraft
- Jae H. Kang
- Alex W. Hewitt
- David A. Mackey
- Jamie E. Craig
- Janey L. Wiggs
- Jue-Sheng Ong
- Stuart MacGregor
- Puya Gharahkhani
1 Application
| Application ID | Title |
|---|---|
| 25331 | Gene mapping and genetic correlation across complex traits |
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