Genetics and glaucoma: Family matters
If a person has a family history of glaucoma, his/her risk of developing the disease increases markedly. But what is the risk? And what is the science behind it? Here, Associate Professor of Ophthalmology at University of Auckland Andrea Vincent shares her expertise on genetics and glaucoma.
Understanding your risk factors for glaucoma may allow for an earlier diagnosis, and for many people, one of the simplest, known risk factors is a family history.
In primary open angle glaucoma (POAG), 4-16% have a positive family history. However, this is unreliable as many cases of glaucoma are not diagnosed and some patients don’t inform their family members that they are affected.
In the Ocular Hypertension Study, 42% had a positive family history in any relative, and in the POAAGG (Primary Open-Angle African American Glaucoma Genetics) study, >35% of subjects had a positive family history in a first degree relative (parent, sibling, child).
Looking at it another way, in one study first degree relatives of patients with POAG had a 22% lifetime risk of developing glaucoma, compared with those in a control population, whose relatives only had a 2.4% risk. An Australian study showed a 9-fold increased risk compared with the general population for first degree relatives of POAG.
We also know that individuals with a family history are more likely to access screening for glaucoma, and at an earlier age.
The Australia and New Zealand Registry of Advanced Glaucoma (ANZRAG) looked at patients diagnosed with glaucoma genetically, vs. those diagnosed in the clinic. In the genetic patients, 83% were unaffected, and the rest were glaucoma suspects. Compare this with the clinical cases, where 44% were glaucoma suspects, 28% had glaucoma, and 22% had advanced glaucoma. The IOP (intraocular pressure) was higher in the clinical cases, and the genetic group was on average 7 years younger than the clinical group.
This demonstrates that knowledge of disease in a family results in earlier screening, and earlier diagnosis.
Personalised medicine is an evolving field, with the potential to use genetic information to predict disease development, and to tailor preventative intervention for an individual. Glaucoma genetics can allow family risk assessment, highlight optimal treatments, and provide new insights into the pathways leading to glaucoma. Ultimately, these genetic targets and pathways may provide opportunity for new treatments.
For juvenile onset open angle glaucoma (JOAG), which affects people under 40 years old, the first gene identified was Myocilin. Although Myocilin only accounts for 2.4% of overall glaucoma, it is responsible for up to 36% of people with JOAG, who often have higher pressures at a younger age and more advanced disease when diagnosed.
Only a few genes like Myocilin exist, where there is a strong correlation between a gene mutation and developing glaucoma. The majority of over 100 glaucoma risk genes individually have a very minor effect on disease development.
Recent studies have summated these genetic risk factors to create a ‘polygenic risk score’. This means that if you have an excess of risk variants, although individually they may not account for much, combined they can predict an earlier onset of disease and greater risk of disease development, compared with those who have fewer risk variants.
So what are the practical considerations of this? Ask your family members if they have glaucoma, and if so, get your eyes checked sooner.
If you have been diagnosed with glaucoma, share this information and encourage your family to get their eyes checked.
Participation in the Australia New Zealand Registry of Advanced Glaucoma (ANZRAG) is free, and can be facilitated by your Eye Specialist, so ask them if you would like to become involved.