Hélène Choquet is a staff scientist at Kaiser Permanente’s Division of Research in Oakland, California. Hélène’s primary interests focus on human genetics, especially the genetics of vision disorders, including glaucoma, and response to its treatments.
Glaucoma causes an increase in eye pressure that damages the optic nerve, which may lead to blindness. Glaucoma occurs five times more often in African Americans than other groups, due in part to genetic factors, and is the leading cause of blindness among African Americans. In 2018, Kaiser Permanente researchers, including Dr. Choquet, analyzed the genes of 65,000 KPRB participants to better understand what causes glaucoma. They uncovered nine new regions in the human genome (loci) that were associated with the risk of developing the most common type of glaucoma. These newly identified loci can explain some of the reasons why African Americans are at higher risk for glaucoma. By identifying these loci, scientists hope to develop better screening tests and treatments that can benefit Kaiser Permanente members and the community at large.
The following interview focuses on Dr. Choquet’s work on the genetics of glaucoma. More information about her work can be found here: https://divisionofresearch.kaiserpermanente.org/researchers/choquet-helene
Why were you interested in studying glaucoma specifically?
Glaucoma is a key cause of blindness in the world. In fact, it is second only to cataracts as a cause of blindness worldwide. Furthermore, I have a personal interest in glaucoma because it runs in my family –both my grandfather and father have been diagnosed with it.
In lay terms, what was your hypothesis about glaucoma and how did you make your discovery?
Glaucoma has an important genetic component. Scientists estimate that genetic factors make up 42% of the reason why someone might get this disease. Prior to our study, only 17 genetic risk factors had been identified but scientists thought that there were other genetic factors that could explain a patient’s susceptibility to glaucoma. Even after our discoveries, we believe there are more genes that could be discovered with bigger cohorts and more diversity.
What does your discovery mean for people who are at risk for glaucoma? How soon can we expect new screening tests or new treatments?
We identified and confirmed 9 regions in the human genome that were not previously known to be associated with glaucoma. There is often a lot of time between scientists making a discovery and new medical treatments. Because we were able to validate these discoveries, these genes are good targets for developing medications and new treatments. The clinical trial process is slow and careful and occurs in 3 stages.
Because we know about genetic factors linked to glaucoma in a broader population, it is possible to create a genetic screening tool to identify more patients who are at high risk for glaucoma. This means that these patients could be identified before they have glaucoma and start preventative treatment, reducing possible optic nerve damage.
Why do some genes impact particular ethnic groups more than other groups? Why is it important to have specimens from many different people?
Glaucoma occurs more often in African Americans than other ethnic groups. Before our study, there was a lack of glaucoma genetic studies for individuals of African ancestry—only people of European or Asian ancestry had been studied. We were the first study to include individuals from additional ethnic backgrounds. We found that some of the higher disease prevalence in African Americans is explained by genetic factors. Other factors could be non-genetic such as diet, culture, and access to healthcare.
The diversity of our study population is an asset because it allows us to find risk factors that are relevant to these populations. Previously known genetic risk factors explain very little of the risk of glaucoma in African Americans. Our study, for the first time, enables us to explain as much of the genetic risk of glaucoma for African Americans as for other populations.
Why did you decide to become a genetic researcher? Why are big diverse cohorts important for your work?
I always wanted to learn more about science and nature. While studying for my bachelor’s degree, the first complete sequencing of all the nucleotides in the human genome was published. Following this important scientific discovery, I became more interested in human genetics and took every class that was related to the subject. Then, I completed a summer internship at the French National Center for Scientific Research studying the role of genetics in obesity and Type 2 Diabetes, and I just loved it! That was the beginning of everything for me.
To identify strong associations between genetic factors and disease traits, it’s important to have samples from a large group of individuals in order to find statistically significant patterns. If we only have samples from individuals of European ancestry, we could miss important genes present in other ancestry populations. This is important because risk and response to treatment can differ among individuals of different ethnicity for many conditions, and especially for glaucoma. Undertaking studies in ethnically diverse populations is essential if we are going to identify and address these population differences.