Genes GSAP and GRM5/TYR were found to be associated with both PDS and PG. Photo: National Cancer Institute on Unsplash (https://unsplash.com/@nci).

A team of researchers recently identified a set of genes that are associated risk factors for the development of pigment dispersion syndrome (PDS) and pigmentary glaucoma (PG), the first of which is a precursor to the latter and to glaucomatous damage. The findings from this meta-analysis of genetic data also suggest that myopia, a known risk factor for glaucoma, may be a cause of both PDS and PG.

The researchers conducted genome-wide association analyses in each of four separate cohorts (all of which were of European ancestry). They performed two-sample Mendelian randomization to determine if there was causal inference between myopia and intraocular pressure over PDS. A total of 574 patients had either PDS or PG, while 52,627 patients acted as controls. The data was then meta-analyzed in three stages:

• First: discovery meta-analysis was performed on three cohorts

• Second: replication was performed on the fourth cohort

• Third: all four cohorts were meta-analyzed

The analyses found that two loci were significantly associated with the presence of PDS/PG. The first, called GSAP, had an odds ratio of 1.83 and a corresponding relative risk of approximately 1.21 per allele; the second (known as GRM5/TYR) had a slightly weaker association but was confirmed from findings of the four-cohort meta-analysis to be significant. There were no additional loci found to be associated with genome-wide significance.

This the first such study “to identify genetic factors significantly associated with PDS among sporadic cases,” the researchers wrote in their paper. “A third gene, FAM83D, is associated with PDS in one of our gene-based analyses and introduces an interesting, novel candidate for further research.”

Interestingly, the researchers also found a significant genetic correlation between PDS and primary open-angle glaucoma (POAG), although the lead SNPs associated with neither PDS nor PG were found to be associated with POAG. “This indicates that the strongest genetic risk factors for both diseases are specific to their respective condition, but there is some shared genetic architecture through genes of lower effect size,” they wrote. “An alternative possibility is that the POAG cases in previous GWAS may include PG patients, as some PDS cases undergo a ‘burn out’ phase during middle age.”

In conclusion, the researchers wrote that data from this meta-analysis provides “strong evidence for two genomic loci and suggestive evidence for a third associated with PDS and PG,” and “demonstrates that myopia exerts direct causal effects in the development of PDS and PG.”