Using Genetics for Glaucoma Screening and Risk Stratification: The LXXXII Edward Jackson Memorial Lecture.

PURPOSE

To provide an update on advances in glaucoma genetics and to describe how genetic information can be used for disease screening and risk stratification.

DESIGN

Perspective and retrospective review.

METHODS

Literature review and personal recollections.

RESULTS

Supported by cutting-edge genetic resources and methodologies as well as collaborations, the field of glaucoma genetics has seen tremendous progress over the past 3 decades with the discovery of at least 11 genes responsible for childhood glaucoma and hundreds of genomic loci influencing adult-onset glaucoma risk. These discoveries are an important step toward a personalized treatment approach for glaucoma and particularly have created opportunities to use this genetic information for glaucoma risk stratification and disease screening. Genetic testing using known glaucoma genes for childhood forms of glaucoma can inform genetic counseling and develop risk-appropriate surveillance and treatment plans for mutation carriers. The overall diagnostic yield for childhood glaucoma is limited by the relatively small number of known genes; however, ongoing research supporting further gene discovery is promising. Hundreds of genetic variants influencing adult-onset glaucoma have been identified by genome-wide association studies, and polygenic risk scores composed of these risk variants have been associated with earlier and more aggressive disease supporting a role for polygenic risk score testing in disease risk stratification and potentially also in population screening.

CONCLUSIONS

Recent advances in glaucoma genetics are providing new opportunities to use genetic information to guide prevention, diagnosis, and treatment of disease and ultimately to develop a personalized approach to glaucoma clinical care.