Glaucoma and Alzheimer’s disease Polygenic Risk Scores within Lifelines

Primary open-angle glaucoma (POAG) is a complex adult-onset polygenic optic neuropathy. There have been several genome-wide association studies (GWAS) completed1, and currently there are more than 65 single nucleotide polymorphisms (SNPs) associated with glaucoma in Caucasian populations2. Current treatment for POAG is the reduction of intra-ocular pressure (IOP) which has shown to be insufficient to stop progression possibly due to the involvement of the brain. Previous studies have delineated neuroanatomical changes in the optic nerve, posterior visual pathway but also beyond the visual system3,4,5. This suggests a trans-synaptic spread of pathology to multiple parts of the brain. Neuropathological similarities between glaucoma and Alzheimer’s disease (AD) further support the hypothesis that glaucoma may be a more widespread neurodegenerative disease instead of affecting the eye only. In fact, epidemiological studies suggest glaucoma to be a strong predictor for AD and that there may be some comorbidity6,7. Several genetic variants associated with POAG appear to be functionally implicated in neurological conditions such as AD2. Our preliminary findings suggest high correlations between polygenic risk scores for POAG and AD only in a small subset of subjects of the Groningen Longitudinal Glaucoma Study (GLGS) – a large cohort of genotyped glaucoma patients9. To further investigate this association in glaucoma as well as healthy subjects we request access to the UGLI GWAS dataset.