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Large study reveals 127 glaucoma genes

In the largest genome-wide association study of glaucoma, an international consortium of researchers has identified 44 new gene loci and confirmed 83 previously reported loci linked to glaucoma.


Primary open-angle glaucoma (POAG) is the leading cause of irreversible blindness worldwide. It is characterised by progressive optic nerve degeneration that is typically accompanied by elevated intraocular pressure. Current therapies are limited to lowering intraocular pressure to try and slow disease progression. However, over 50% of glaucoma is not diagnosed until irreversible optic nerve damage has occurred.

POAG is highly heritable. Previous GWAS have identified important loci associated with POAG risk. Nonetheless, the POAG genetic landscape remains incomplete. The identification of additional risk loci is important to further define disease mechanisms that could be targeted by preventative therapies.

In addition, majority of known risk loci for POAG have been found through GWAS in participants of European descent. Observational studies have shown that individuals of African ancestry, followed by Latinos and Asians, have higher POAG disease burden compared to those with European ancestry. This emphasises the importance of comparing the genetic architecture of these ethnic groups.

Large GWAS

In this study, published in Nature Communications, researchers conducted a multi-ethnic meta-analysis on 34,179 POAG cases and 349,321 controls. Here, the team identified 127 risk loci – 44 of which were not previously reported at genome-wide significance levels for POAG. These identified risk loci had broadly consistent effects across European, Asian and African ancestries. They showed that combining GWAS data across ancestries improved fine mapping of the most likely causal variants for some loci.

Additionally, the integration of multiple lines of genetic evidence supported the functional relevance of the POAG risk loci, identifying the most likely causal genes. These included SVEP1, RERE, VCAM1, ZNF638, CLIC5, SLC2A12, YAP1, MXRA5, and SMAD6. Some of these genes may contribute to glaucoma pathogenesis through biological mechanisms related to extracellular matrix cell adhesion, intracellular chloride channels, adipose metabolism and YAP/HIPPO signalling.

Professor Stuart MacGregor, co-senior researcher on the study, stated:

“Glaucoma is one of the most strongly genetic human diseases, which is why we are looking at the genetic architecture of the disease to find clues on how to prevent and treat it.

We’re hopeful that understanding the biological processes and knowing which genes control them could help scientists develop new drugs in the future.”

Image by Pexels from Pixabay

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Cancer / Glaucoma / GWAS