Identifying Novel Genetic Loci associated with Primary Open-Angle Glaucoma

Abstract

Purpose : Glaucoma is one of the most frequent causes of irreversible blindness caused by optic nerve degeneration. Currently, over 20 loci have been identified through multiple genome-wide association studies (GWAS). However, only about 10% of phenotypic variations can be explained by these loci combined, underscoring the need of further investigation of genetic risk factors of POAG.

Methods : In this study, we reanalyzed several previously published genome-wide association studies for POAG, including the Glaucoma Genes and Environment (GLAUGEN), National Eye Institute (NEI) Glaucoma Human Genetics Collaboration (NEIGHBOR), and the Chinese high tension open angle glaucoma study, using a combination of individual SNP and local haplotype sharing (LHS) methods. Candidate SNPs and loci are further validated by genotyping additional 1000 cases. Functional testing of selected candidate genes and loci is performed using animal model.

Results : In this study, we identified several recently reported POAG-associated loci such as TXNRD2, FOXC1, and FNDC3B indicating our approach is effective. More interestingly, more than 10 novel candidate loci were identified by either the single SNP test or the LHS method. Among them, GLIS3 and TRPM3 genes have been linked to congenital glaucoma but have not yet been associated with adult onset POAG. In addition, at least 3 candidate loci have been confirmed in our validation cohort.

Conclusions : Our study identifies a set of novel candidate POAG associated loci, some of which have been confirmed. Functional studies of these novel loci/gene will provide additional insights of the disease.

This is an abstract that was submitted for the 2018 ARVO Annual Meeting, held in Honolulu, Hawaii, April 29 - May 3, 2018.