Summary

Glaucoma is the leading cause of irreversible blindness in the world. Raised intraocular pressure (IOP) is the most important modifiable risk factor for primary open-angle glaucoma (POAG). Yet the mechanism underling IOP regulation is not yet understood.  Prior to our study, genome-wide association studies (GWAS) had identified only a few genetic markers associated with IOP, explaining a tiny proportion of its variability.

We carried out a GWAS for IOP in over 100,000 European participants and identified 112 independent loci associated with IOP.  These genetic markers explained 17% of the variance of IOP, which is huge considering the daily variation in IOP in individuals and measurement error which affects IOP readings.

Potential impact for healthcare and innovation

The major risk factor for developing blindness from glaucoma is delayed presentation.  Earlier diagnosis of people at risk is key to preventing blindness.  However, current screening tests are not sufficiently effective to warrant general population screening (there are too many false positives).  Glaucoma case finding in the UK is therefore only opportunistic and late presentation resulting in blindness still occurs.  Excitingly, we showed that the genetic variants we identified had 75% predictive power for POAG.  This means, even before any ophthalmic assessment, these genetic markers can identify people within a population that are at risk of glaucoma.  Targeting these high-risk people may make current glaucoma screening tests effective (less false positives), enable earlier diagnosis and treatment, and prevent irreversible vision loss.

All the novel genes and pathways we identified as regulating IOP are potential targets for new glaucoma treatments. 

• Anthony P. Khawaja, Jessica N. Cooke Bailey, Nicholas J. Wareham, Robert A. Scott, Mark Simcoe, Robert P. Igo Jr, Yeunjoo E. Song, Robert Wojciechowski, Ching-Yu Cheng, Peng T. Khaw, Louis R. Pasquale, Jonathan L. Haines, Paul J. Foster, Janey L. Wiggs, Chris J. Hammond, Pirro G. Hysi, UK Biobank Eye and Vision Consortium & NEIGHBORHOOD Consortium. Genome-wide analyses identify 68 new loci associated with intraocular pressure and improve risk prediction for primary open-angle glaucoma