GWAS meta-analysis finds over forty new risk loci for POAG

A recent meta-analysis of genome-wide association studies (GWAS) has identified new and validated known genetic loci for primary open-angle glaucoma (POAG). Majority of the risk loci have consistent effects across different ancestries.

The meta-analysis included 34,179 POAG cases and 349,321 controls across three major ethnic backgrounds: Asian, African, and European. A total of 127 independent genome-wide significant risk loci were identified, each located >1 Mb apart.

Notably, 44 of these loci were novel and had never been associated with POAG to a genome-wide significant degree.

In addition, four risk loci (MXRA5-PRKX, GPM6B, NDP-EFHC2, and TDGF1P3-CHRDL1) were located in the X-chromosome, representing the first such POAG-associated loci on a sex chromosome.

In terms of function, 89 of 123 POAG risk loci were also associated with intraocular pressure (IOP); four loci were unavailable for analysis for IOP. Of the remaining 34 genetic loci, 24 showed a clear interaction with vertical cup-to-disc ratio (VCDR). Both IOP and VCDR are known heritable endophenotypes linked to POAG.

“In this large multi-ethnic meta-analysis for POAG, we identified 127 risk loci for POAG, of which 44 were not previously identified,” the researchers said. “The risk loci include genes that are highly expressed in relevant eye tissues, nerves, arteries, as well as tissues enriched with these components.

“Further studies to investigate the biological roles of these risk loci with respect to POAG pathogenesis in relevant eye tissues will further shed light on the molecular aetiology of POAG,” they added.