| Title: | GWAS-by-subtraction reveals an IOP-independent component of primary open angle glaucoma |
| Journal: | Nature Communications |
| Published: | 17 Oct 2024 |
| Pubmed: | https://pubmed.ncbi.nlm.nih.gov/39419966/ |
| DOI: | https://doi.org/10.1038/s41467-024-53331-0 |
Publication 13421
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Abstract
The etiology of primary open angle glaucoma is constituted by both intraocular pressure-dependent and intraocular pressure-independent mechanisms. However, GWASs of traits affecting primary open angle glaucoma through mechanisms independent of intraocular pressure remains limited. Here, we address this gap by subtracting the genetic effects of a GWAS for intraocular pressure from a GWAS for primary open angle glaucoma to reveal the genetic contribution to primary open angle glaucoma via intraocular pressure-independent mechanisms. Seventeen independent genome-wide significant SNPs were associated with the intraocular pressure-independent component of primary open angle glaucoma. Of these, 7 are located outside known normal tension glaucoma loci, 11 are located outside known intraocular pressure loci, and 2 are novel primary open angle glaucoma loci. The intraocular pressure-independent genetic component of primary open angle glaucoma is associated with glaucoma endophenotypes, while the intraocular pressure-dependent component is associated with blood pressure and vascular permeability. A genetic risk score for the intraocular pressure-independent component of primary open angle glaucoma is associated with 26 different retinal micro-vascular features, which contrasts with the genetic risk score for the intraocular pressure-dependent component. Increased understanding of these intraocular pressure-dependent and intraocular pressure-independent components provides insights into the pathogenesis of glaucoma.</p>
10 Keywords
- Blood Pressure
- Female
- Genetic Predisposition to Disease
- Genome-Wide Association Study
- Glaucoma, Open-Angle
- Humans
- Intraocular Pressure
- Male
- Middle Aged
- Polymorphism, Single Nucleotide
14 Authors
- Yu Huang
- Denis Plotnikov
- Huan Wang
- Danli Shi
- Cong Li
- Xueli Zhang
- Xiayin Zhang
- Shulin Tang
- Xianwen Shang
- Yijun Hu
- Honghua Yu
- Hongyang Zhang
- Jeremy A. Guggenheim
- Mingguang He
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