Glaucoma Genetic Risk scores within Lifelines

Primary open-angle glaucoma is a complex adult-onset polygenic ophthalmic disorder. There have been several genome-wide association studies (GWAS) completed, and currently there are more than 65 single nucleotide polymorphisms (SNPs) associated with glaucoma in Caucasian populations. GWAS have also been performed on glaucoma-related endophenotypes, such as intraocular pressure (IOP), central corneal thickness (CCT), vertical cup to disc ratio (VCDR) etc. The significant SNPs from these various GWAS were creatively combined into a genetic risk score (GRSs) for glaucoma; the most recent and largest glaucoma GWAS was used to obtain the “glaucoma effect”.¹ The objective of our recently started EyeLife study already approved by METC and Lifelines is to see if pre-screening for glaucoma based on genetic risk is feasible in a population-based cohort. Lifelines participants with the highest and lowest 20% of genetic risk for glaucoma have been invited to be phenotyped in the newly developed EyeLife clinic. Currently, the pool of participants from which we can draw and invite subjects for ocular phenotyping is limited to the currently available 13,000 genotyped participants, moreover, we have restricted invites to those within a 10km circumference to the UMCG. As such we request access to the larger UGLI GWAS dataset in order to expand our pool of Lifelines participants from which we can select those belonging to the upper or lower 20% of their glaucoma GRS.