A common variant near TGFBR3 is associated with primary open angle glaucoma

Area of Science:

• Genetics
• Ophthalmology
• Genomic Epidemiology

Background:

• Primary open angle glaucoma (POAG) is a leading cause of global blindness.
• POAG has a substantial genetic component, necessitating further research into its genetic architecture.
• Previous genetic studies have identified some risk loci, but much of the genetic basis remains unexplained.

Purpose of the Study:

• To identify novel genetic variants associated with primary open angle glaucoma (POAG).
• To confirm previously identified genetic associations with POAG across diverse ancestries.
• To investigate the role of specific genetic loci in POAG pathogenesis.

Main Methods:

• Exome array analysis was conducted on a large cohort of POAG cases and controls.
• Replication analysis was performed across multiple international collections of European, Asian, and African descent.
• Genome-wide association study (GWAS) meta-analysis was used to identify significant genetic associations.

Main Results:

• Strong evidence of association was confirmed for the CDKN2B-AS1 locus (rs2157719).
• A novel significant association was found for the CDC7-TGFBR3 locus (rs1192415) with POAG.
• The identified SNP rs1192415 is also associated with optic disc area and vertical cup-to-disc ratio, key glaucoma-related traits.

Conclusions:

• The study implicates the CDC7-TGFBR3 locus in the pathogenesis of primary open angle glaucoma.
• These findings expand the known genetic risk factors for POAG.
• The genetic associations identified contribute to understanding the biological mechanisms underlying POAG.