Study investigates association of monogenic and polygenic risk with glaucoma prevalence
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Individuals with a high polygenic risk for glaucoma have similar likelihood to develop the disease as those with the most common single-gene pathogenic variant and at an equivalent age, according to a study.
Polygenic risk was also found to be 15 times higher in the general population than the single-gene variant.
Out of 2,507 individuals included in the Australian and New Zealand Registry of Advanced Glaucoma (ANZRAG), 109 were identified as monogenic, presenting a pathogenic heterozygous variant in the myocilin (MYOC) gene, the most common glaucoma-causing gene. Of all MYOC variants, p.Gln368Ter was the most prevalent, accounting for 2.6% of all glaucoma cases.
Following genome-wide genotyping, 1,366 individuals in the same registry were then assigned a glaucoma polygenic risk score (PRS). Individuals at high polygenic risk were defined as those in the top 5% of an unselected population. As compared with an ancestrally matched control population, the ANZRAG non-monogenic glaucoma population had an increased PRS, which was not significantly different compared with individuals heterozygous for MYOC p.Gln368Ter nor other pathogenic MYOC variants. In addition, the age at which at-risk individuals developed glaucoma did not differ statistically between individuals with glaucoma PRS in the top 5% and individuals heterozygous for MYOC p.Gln368Ter. The polygenic risk, however, was found to be 15 times more common in the general population as compared with the singe-gene variant.
The authors suggested that PRS might be a valuable tool to improve risk stratification in glaucoma, a disease that often remains undetected until the patients perceive the symptoms of irreversible vision loss.
“The use of genetic risk stratification may be a valuable screening adjunct, allowing higher-risk individuals to be monitored earlier and more frequently, and lower-risk individuals later and less frequently. Importantly, a glaucoma PRS can provide additional predictive ability on top of traditional risk factors, including age, sex and self-reported family history,” the authors wrote.
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