Primary open-angle glaucoma (POAG), the leading cause of irreversible blindness worldwide, disproportionately affects African Americans. Large-scale POAG genetic studies have focused on individuals of European and Asian ancestry, limiting our understanding of disease biology. Here we report genetic analysis of the largest-ever deeply phenotyped African American population (n=5950), identifying a novel POAG-associated SNP on chromosome 11 near the TRIM66 gene (rs112369934). POAG trait association also implicated SNPs in genes involved in trabecular meshwork homeostasis and retinal ganglion cell maintenance. These new loci deepen our understanding of the pathophysiology of POAG in African Americans.

Strand specific RNA sequencing of retina and RPE-Choroid-Scleara (RCS) in age-related macular degeneration (AMD) and matched normal controls reveals striking impact on anti-sense transcription and changes in the regulation of non-coding RNA that has not previously been reported. Hundreds of genes, which do not express anti-sense transcripts in normal retina and RCS, demonstrate extreme anti-sense expression in AMD. And conversely anti-sense transcription is completely abrogated in many genes which express a high level of anti-sense transcripts in normal retina and RCS. Several pathways are very highly enriched in the upregulated anti-sense transcripts -in particular the EIF2 signaling pathway. These results call for a deeper investigation into anti-sense and noncoding RNA regulation in AMD and their potential as therapeutic targets.