Genome-wide meta-analysis identifies 127 open-angle glaucoma loci with consistent effect across ancestries

Area of Science:

• Ophthalmology
• Genetics
• Genomics

Background:

• Primary open-angle glaucoma (POAG) is a significant heritable cause of global blindness.
• Identifying genetic risk factors is crucial for understanding POAG pathogenesis and developing treatments.

Purpose of the Study:

• To conduct a large-scale, multi-ethnic genome-wide association study (GWAS) meta-analysis to identify novel genetic risk loci for POAG.
• To confirm previously known POAG risk loci and investigate the consistency of genetic effects across diverse ancestries.

Main Methods:

• A meta-analysis of GWAS data from 34,179 POAG cases and 349,321 controls across multiple ancestries.
• Integration of various genetic evidence to support the functional relevance of identified risk loci.

Main Results:

• Identification of 44 novel POAG risk loci, in addition to confirming 83 previously known loci.
• Demonstration of broadly consistent effect sizes for most loci across European, Asian, and African ancestries.
• Fine-mapping of causal variants was improved using cross-ancestry data.

Conclusions:

• Genetic factors play a substantial role in POAG pathogenesis.
• Several genes, including SVEP1, RERE, VCAM1, ZNF638, CLIC5, SLC2A12, YAP1, MXRA5, and SMAD6, are implicated in POAG.
• Drug compounds targeting identified POAG risk genes represent potential therapeutic candidates for glaucoma.