New light on glaucoma gene discoveries

Globally 78 million people have glaucoma. That is one in every 200 people aged 40, which rises to one in eight by age 80 – and rising.

Most people with glaucoma are not aware of it as most glaucoma patients have zero symptoms in the early stages.

Catch the disease early and you have a great chance of preserving your vision for the years to come.

Ahead of World Glaucoma Week (7-13 March 2021, #glaucomaweek), Australian researchers published the largest genetic study of glaucoma identifying 44 new genetic variants that may lead to new treatment targets.

Ten Australian institutions involving some of the country’s most prominent glaucoma researchers – including Matthew Flinders Distinguished Professor Jamie Craig and Flinders University colleagues at the Australian and New Zealand Registry of Advanced Glaucoma (ANZRAG) – were involved in the international effort which analysed genes in more than 34,000 people with glaucoma across multiple ancestries for the first time.

The results comparing the genes of people with the disease to 349,321 control subjects were published in Nature Communications last month.

Professor Craig says the international efforts such as this – analysing data on large numbers of glaucoma cases, incorporating clinical information and DNA – continues to lead to new genetic glaucoma risk profiles.

“Better identification of those people at high risk of glaucoma, through genetic screening, would result in an overall reduction of preventable blindness by treating the condition before serious sight loss has occurred,” he says.

Ophthalmology researchers Dr Emmanuelle Souzeau and Professor Jamie Craig with some of the equipment in the Flinders Eye and Vision Centre.

Glaucoma is the second most prevalent cause of blindness world-wide. Primary open-angle glaucoma is the leading cause of irreversible blindness globally.

In addition to identifying new genetic variants, the international consortium of researchers also confirmed 83 previously reported genetic variants linked to glaucoma. Genetic variants are considered “genetic street addresses”, denoting a specific location on a gene.

Associate Professor Puya Gharahkhani, from Brisbane’s QIMR Berghofer Medical Research Institute, says for the first time in a glaucoma genome-wide association study, this research performed a cross-ancestry comparison looking at genetic data from people of European, African and Asian descent.

This found the majority of loci that contribute to glaucoma were consistent across all three groups.

“Glaucoma rates are highest in African and Asian ancestry groups, but the largest genetic studies of glaucoma in the past focused on people of European ancestry,” he says.

“Those studies showed genetic tests could be used to help identify who would benefit from sight-saving early monitoring or treatment, but because of the narrow scope of the genetic data, we weren’t sure until now that the genetic indicators were true for people of different ancestries.”

Future research will focus on using these genetic loci to improve screening and diagnosis of glaucoma and, one day, to develop new treatments.

“Glaucoma is one of the most strongly genetic human diseases, which is why we are looking at the genetic architecture of the disease to find clues on how to prevent and treat it,” adds Professor Stuart MacGregor, the head of QIMR Berghofer’s Statistical Genetics group and co-senior researcher on the study.

“We’re hopeful that understanding the biological processes and knowing which genes control them could help scientists develop new drugs in the future.”

Institutions that participated in the study included Flinders University Ophthalmology at Flinders Medical Centre, and the South Australian Institute of Ophthalmology at the University of Adelaide in South Australia, and in NSW the Centre for Vision Research, Department of Ophthalmology and Westmead Institute for Medical Research at the University of Sydney; Ophthalmology and Vision Science at Macquarie University; and Department of Ophthalmology at the University of Sydney, Sydney Eye Hospital.

Others were the Menzies Institute for Medical Research at the University of Tasmania; the Centre for Eye Research Australia at the University of Melbourne; the Centre for Ophthalmology and Visual Science at the University of Western Australia; and QIMR Berghofer Medical Research Institute in Brisbane.

Grants from the National Health and Medical Research Council (NHMRC) of Australia and the Ophthalmic Research Institute of Australia helped support the study.

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