Yutao Liu, Augusta University
Jessica Cooke Bailey, Case Western Reserve University
Inas Helwa, Augusta University
W. Michael Dismuke, Duke University
Jingwen Cai, Augusta University
Michelle Drewry, Augusta University
Murray H. Brilliant, Marshfield Clinic Research Foundation
Donald L. Budenz, University of North Carolina at Chapel Hill
William G. Christen, Brigham and Womens Hospital
Daniel I. Chasman, Brigham and Women’s Hospital
John H. Fingert, University of Iowa
Douglas Gaasterland, The Emmes Corporation
Terry Gaasterland, University of California at San Diego
Mae O. Gordon, Washington University School of Medicine
Robert P. Igo Jr., Case Western Reserve University
Jae H. Kang, Brigham and Women’s Hospital
Michael A. Kass, Washington University School of Medicine
Peter Kraft, Harvard University
Richard K. Lee, University of Miami
Paul Lichter, The University Of Michigan
Sayoko E. Moroi, The University Of Michigan
Anthony Realini, West Virginia University
Julia E. Richard, The University Of Michigan
Robert Ritch, New York Eye and Ear Infirmary of Mount Sinai
Joel S. Schuman, University of Pittsburgh
William K. Scott, University of Miami
Kuldev Singh, Stanford University
Arthur J. Sit, Mayo Clinic
Yeunjoo E. Song, Case Western Reserve University
Douglas Vollrath, Stanford University
Robert Weinreb, University of California - San Diego
Felipe Medeiros, University of California - San Diego
Gadi Wollstein, University of Pittsburgh
Donald J. Zack, Johns Hopkins University Hospital
Kang Zhang, University of California - San Diego
Margaret A. Pericak-Vance, University of Miami
Pedro Gonzalez, Duke University
W. Daniel Stamer, Duke University
John Kuchtey, Vanderbilt University Medical Center
Rachel W. Kuchtey, Vanderbilt University Medical Center
R. Rand Allingham, Duke University Medical Center
Michael A. Hauser, Duke University Medical Center
Louis R. Pasquale, Mass Eye & Ear
Jonathan L. Haines, Case Western Reserve University
Janey L. Wiggs, Mass Eye & Ear

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School of Medicine




PURPOSE. Noncoding microRNAs (miRNAs) have been implicated in the pathogenesis of glaucoma. We aimed to identify common variants in miRNA coding genes (MIR) associated with primary open-angle glaucoma (POAG).

METHODS. Using the NEIGHBORHOOD data set (3853 cases/33,480 controls with European ancestry), we first assessed the relation between 85 variants in 76 MIR genes and overall POAG. Subtype-specific analyses were performed in high-tension glaucoma (HTG) and normal-tension glaucoma subsets. Second, we examined the expression of miR-182, which was associated with POAG, in postmortem human ocular tissues (ciliary body, cornea, retina, and trabecular meshwork [TM]), using miRNA sequencing (miRNA-Seq) and droplet digital PCR (ddPCR). Third, miR-182 expression was also examined in human aqueous humor (AH) by using miRNA-Seq. Fourth, exosomes secreted from primary human TM cells were examined for miR-182 expression by using miRNA-Seq. Fifth, using ddPCR we compared miR182 expression in AH between five HTG cases and five controls.

RESULTS. Only rs76481776 in MIR182 gene was associated with POAG after adjustment for multiple comparisons (odds ratio [OR] ¼ 1.23, 95% confidence interval [CI]: 1.11–1.42, P ¼ 0.0002). Subtype analysis indicated that the association was primarily in the HTG subset (OR ¼ 1.26, 95% CI: 1.08–1.47, P ¼ 0.004). The risk allele T has been associated with elevated miR-182 expression in vitro. Data from ddPCR and miRNA-Seq confirmed miR-182 expression in all examined ocular tissues and TM-derived exosomes. Interestingly, miR-182 expression in AH was 2-fold higher in HTG patients than nonglaucoma controls (P ¼ 0.03) without controlling for medication treatment.

CONCLUSIONS. Our integrative study is the first to associate rs76481776 with POAG via elevated miR-182 expression.

Source Citation

Liu, Y., Bailey, J. C., Helwa, I., Dismuke, W. M., Cai, J., Drewry, M., Brilliant, M. H., Budenz, D. L., Christen, W. G., Chasman, D. I., Fingert, J. H., Gaasterland, D., Gaasterland, T., Gordon, M. O., Igo, R. P., Jr, Kang, J. H., Kass, M. A., Kraft, P., Lee, R. K., … Wiggs, J. L. (2016). A Common Variant in MIR182 Is Associated With Primary Open-Angle Glaucoma in the NEIGHBORHOOD Consortium. Investigative Opthalmology & Visual Science, 57(10), 4528.


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