A new study led by Dr Robert Luben at the University of Cambridge, utilizing data from European and Asian studies including EPIC-Norfolk and UK Biobank, has identified genetic risk factors for primary angle-closure glaucoma (PACG) in European populations, shedding new light on the genetic underpinnings of this condition across different ancestry groups.

In PACG the eye’s drainage angle becomes blocked, leading to increased pressure in the eye and damage to the optic nerve. It is a leading cause of blindness in older adults, and while most cases are reported in East Asian populations, an estimated 2.6 million people of European ancestry have PACG. Previous genome-wide association studies (GWAS) identified eight genetic loci associated with PACG risk in Asian populations. However, the extent to which these genetic risk factors apply to other populations has remained unclear.

In this new study, researchers conducted a discovery GWAS for PACG in European populations using data from the UK Biobank, identifying five genomic regions that were associated with PACG, including two loci previously identified in Asian populations. They successfully replicated their findings in six independent European populations and then compared these results with data from 14 Asian population cohorts.

The meta-analysis that statistically combined data from the combined European and Asian populationcohorts identified six additional novel loci, all previously associated with refractive error, a common eye condition where the eye cannot focus light properly on the retina, leading to blurred vision

Using Mendelian randomisation, the study provided strong evidence for a causal role of shorter axial length of the eye and hypermetropic (farsighted) refractive error in the development of PACG. Furthermore, a polygenic risk score derived from the European ancestry meta-analysis showed significant associations with quantitative ocular traits, such as a shallower anterior chamber and higher intraocular pressure, in the EPIC-Norfolk eye cohort.

In a subsequent multi-ancestry meta-analysis of 21 European and Asian cohorts, the researchers identified 12 additional novel loci. Most notably, the study showed that genetic factors associated with a darker iris eye axial length and hypermetropia confer risk for primary angle-closure glaucoma. Genetic factors associated with a darker iris were associated with PACG in European but not Asian populations, potentially reflecting the more homogeneous eye colour in Asian populations, and eye colour may be a surrogate for other genetic risk factors such as iris thickness.

This research not only advances our understanding of the genetic basis of PACG, opening up the possibility of targeted screening efforts for this blinding disease, but also highlights the importance of considering genetic diversity across populations in the study of complex diseases.

Reference

• Robert N. Luben et al. GWAS for primary angle-closure glaucoma identifies loci related to ocular biometry and morphology. Nature Communications (2025). DOI:10.1038/s41467-025-64949-z