Mechanosensitive ion channel gene survey suggests potential roles in primary open angle glaucoma
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Published:2023-09-23
Issue:1
Volume:13
Page:
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ISSN:2045-2322
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Container-title:Scientific Reports
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language:en
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Short-container-title:Sci Rep
Author:
Liu Wendy W., Kinzy Tyler G., Cooke Bailey Jessica N.ORCID, Xu Zihe, Hysi PirroORCID, Wiggs Janey L.ORCID, Allingham R. Rand, Brilliant Murray, Budenz Donald L., Fingert John H., Gaasterland Douglas, Gaasterland Teresa, Haines Jonathan L., Hauser Michael A., Lee Richard K., Lichter Paul R., Liu Yutao, Moroi Syoko, Myers Jonathan, Pasquale Louis R., Pericak-Vance Margaret, Realini Anthony, Rhee Doug, Richards Julia E., Ritch Robert, Schuman Joel S., Scott William K., Singh Kuldev, Sit Arthur J., Vollrath Douglas, Weinreb Robert N., Wollstein Gadi, Zack Donald J.,
Abstract
AbstractAlthough glaucoma is a disease modulated by eye pressure, the mechanisms of pressure sensing in the eye are not well understood. Here, we investigated associations between mechanosensitive ion channel gene variants and primary open-angle glaucoma (POAG). Common (minor allele frequency > 5%) single nucleotide polymorphisms located within the genomic regions of 20 mechanosensitive ion channel genes in the K2P, TMEM63, PIEZO and TRP channel families were assessed using genotype data from the NEIGHBORHOOD consortium of 3853 cases and 33,480 controls. Rare (minor allele frequency < 1%) coding variants were assessed using exome array genotyping data for 2606 cases and 2606 controls. Association with POAG was analyzed using logistic regression adjusting for age and sex. Two rare PIEZO1 coding variants with protective effects were identified in the NEIGHBOR dataset: R1527H, (OR 0.17, P = 0.0018) and a variant that alters a canonical splice donor site, g.16-88737727-C-G Hg38 (OR 0.38, P = 0.02). Both variants showed similar effects in the UK Biobank and the R1527H also in the FinnGen database. Several common variants also reached study-specific thresholds for association in the NEIGHBORHOOD dataset. These results identify novel variants in several mechanosensitive channel genes that show associations with POAG, suggesting that these channels may be potential therapeutic targets.
Funder
U.S. Department of Health & Human Services | National Institutes of Health American Glaucoma Society Foundation Research to Prevent Blindness E. Matilda Ziegler Foundation for the Blind Glaucoma Research Foundation
Publisher
Springer Science and Business Media LLC
Subject
Multidisciplinary
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