Project.1 We investigated the association of genetic variants in miRNA-encoding sequences and miRNA-binding sites with Age-related macular degeneration (AMD) using data from the largest genome-wide association study of AMD. We identified 3 variants in miR-4513 seed sequence, in pre-miR-122/miR-3591, and in the terminal-loop of pre-miR-3135b significantly associated with AMD. We demonstrated that these variants reduce expression levels of the mature miRNAs in vitro and pointed the target genes that may mediate downstream effects of these miRNAs in AMD. Also, we identified 54 variants in miRNA-binding sites within 3’UTR of 31 genes to be associated with AMD. Among them, we experimentally showed the SNP in 3’UTR of CFB influences on miR-210-5p-mediated repression of CFB.

Genetic variants in microRNAs and their binding sites within gene 3’UTRs associate with susceptibility to age-related macular degeneration. Ghanbari M, et al. Human Mutation. 2017 Jul;38(7):827-838. doi: 10.1002/humu.23226.

Project.2 By leveraging data from the largest available genome-wide association of on intraocular pressure, vertical cup-to-disc ratio (VCDR), cupa area and disc area, we investigated the association of genetic variants in miRNAs and primary open-angle glaucoma (POAG). Of 411 miRNA variants, SNP in the terminal loop of pre-miR-612 and SNP in the seed sequence of miR-4707 were significantly associated with VCDR and cup area. Moreover, out of 72,052 miRNA-binding-site variants 47 were significantly associated with four POAG endophenotypes. We highlighted 10 variants that were more likely to affect miRNA-mediated gene regulation in POAG.

A Genome-Wide Scan for MicroRNA-Related Genetic Variants Associated With Primary Open-Angle Glaucoma.
Ghanbari M, et al. Invest Ophthalmol Vis Sci. 2017 Oct 1;58(12):5368-5377. doi: 10.1167/iovs.17-22410.