{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,21]],"date-time":"2026-04-21T08:36:20Z","timestamp":1776760580458,"version":"3.51.2"},"reference-count":28,"publisher":"Public Library of Science (PLoS)","issue":"6","license":[{"start":{"date-parts":[[2022,6,28]],"date-time":"2022-06-28T00:00:00Z","timestamp":1656374400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000053","name":"National Eye Institute","doi-asserted-by":"crossref","award":["EY032559"],"award-info":[{"award-number":["EY032559"]}],"id":[{"id":"10.13039\/100000053","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100000053","name":"National Eye Institute","doi-asserted-by":"publisher","award":["K23EY032634"],"award-info":[{"award-number":["K23EY032634"]}],"id":[{"id":"10.13039\/100000053","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100007337","name":"Massachusetts Eye and Ear","doi-asserted-by":"publisher","award":["MEE Institutional Startup Fund"],"award-info":[{"award-number":["MEE Institutional Startup Fund"]}],"id":[{"id":"10.13039\/100007337","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS ONE"],"abstract":"<jats:sec id=\"sec001\">\n<jats:title>Background\/Aims<\/jats:title>\n<jats:p>Psychotropic medications have been reported as a risk factor for angle closure disease. However, the interaction between background genetic risk for primary angle closure glaucoma (PACG) and susceptibility to angle closure disease among psychotropic medication users has not been investigated. Here we demonstrate the utility of a genome-wide polygenic risk score (PRS) in identifying and risk-stratifying subjects with PACG and investigate the association between PACG genetic burden and exposure to psychotropic medications on prevalent angle closure.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec002\">\n<jats:title>Methods<\/jats:title>\n<jats:p>This analysis used the UK Biobank dataset, a prospective cohort study of 502,506 UK residents. We constructed a PACG PRS for participants using genome-wide association study summary statistics from a multiethnic meta-analysis using the Lassosum method.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec003\">\n<jats:title>Results<\/jats:title>\n<jats:p>Among the 441,054 participants, 959 (0.22%) were identified as PACG cases. Individuals with PACG had higher PRS compared to those without PACG (0.24\u00b11.03 SD vs. 0.00\u00b11.00 SD, p&lt;0.001) and PACG prevalence increased with each decile of higher PRS. Among individuals using psychotropic medication, those with PACG had higher average PRS (0.31\u00b11.00 SD vs. 0.00\u00b11.00 SD, p&lt;0.001) and were more likely to have a PRS in upper deciles of polygenic risk (p = 0.04). At each decile of PRS, psychotropic medication use was associated with increased risk of PACG. These effects were more pronounced and significant in higher deciles.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec004\">\n<jats:title>Conclusion<\/jats:title>\n<jats:p>We demonstrate the utility of a PRS for identifying individuals at higher risk of PACG. Additionally, we demonstrate an important relationship where the association between psychotropic medications use and PACG diagnosis varies across the polygenic risk spectrum.<\/jats:p>\n<\/jats:sec>","DOI":"10.1371\/journal.pone.0270530","type":"journal-article","created":{"date-parts":[[2022,6,28]],"date-time":"2022-06-28T18:23:08Z","timestamp":1656440588000},"page":"e0270530","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":7,"title":["Interaction of background genetic risk, psychotropic medications, and primary angle closure glaucoma in the UK Biobank"],"prefix":"10.1371","volume":"17","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6480-8880","authenticated-orcid":true,"given":"Sayuri","family":"Sekimitsu","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jiali","family":"Wang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tobias","family":"Elze","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ayellet V.","family":"Segr\u00e8","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Janey L.","family":"Wiggs","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1763-9401","authenticated-orcid":true,"given":"Nazlee","family":"Zebardast","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"340","published-online":{"date-parts":[[2022,6,28]]},"reference":[{"key":"pone.0270530.ref001","doi-asserted-by":"crossref","first-page":"624179","DOI":"10.3389\/fmed.2020.624179","article-title":"Prevalence of Primary Angle Closure Glaucoma in the Last 20 Years: A Meta-Analysis and Systematic Review","volume":"7","author":"N Zhang","year":"2020","journal-title":"Front Med (Lausanne)."},{"key":"pone.0270530.ref002","doi-asserted-by":"crossref","first-page":"381","DOI":"10.1111\/j.1442-9071.2012.02774.x","article-title":"Angle closure and angle-closure glaucoma: what we are doing now and what we will be doing in the future: Who gets angle-closure, and how important is it? 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