{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,22]],"date-time":"2026-07-22T23:39:39Z","timestamp":1784763579564,"version":"3.55.0"},"reference-count":56,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2024,10,24]],"date-time":"2024-10-24T00:00:00Z","timestamp":1729728000000},"content-version":"vor","delay-in-days":23,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Health Science Reports"],"published-print":{"date-parts":[[2024,10]]},"abstract":"<jats:title>ABSTRACT<\/jats:title><jats:sec><jats:title>Background and Aims<\/jats:title><jats:p>Observational studies suggest that antidiabetic drugs may lower POAG risk; while the causal relationship remains unclear. Naturally occurring variation in genes encoding antidiabetics drug targets can be used as proxies to investigate long\u2010term therapeutic effect of these drugs on POAG risk.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We performed a two\u2010sample Mendelian randomization study to evaluate the potential effect of antidiabetic drug targets on POAG in Europeans and East Asians. To proxy antidiabetic drugs (ABCC8, PPARG, GLP1R, SLC5A2), we leveraged genetic variants located near or within drug target genes that were associated with HbA1c. The validity of our ancestry\u2010specific genetic instrument was checked with multipul positive control outcomes. Genetic summary statistics of POAG from the International Glaucoma Genetics Consortium, Global Biobank Meta\u2010analysis Initiative, and FinnGen consortia were analyzed for Europeans (38,164 cases and 1,576,179 controls) and East Asians (16,650 cases and 288,833 controls) separately. Inverse\u2010variance weighted random\u2010effects models were used as primary method.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>MR results provided consistent evidence of a protective effect of ABCC8 inhibition on POAG using data sets from IGG, GBMI, and FinnGen. Genetically predicted one\u2010standard deviation reduction in HbA1c from ABCC8 inhibition were significant associated with lower risk of POAG in Europeans (OR\u2009=\u20090.211, 95% CI: 0.133\u20130.333; <jats:italic>p<\/jats:italic>\u2009&lt;\u20090.001) and East Asians (OR\u2009=\u20090.070, 95% CI: 0.011\u20130.459; <jats:italic>p<\/jats:italic>\u2009=\u20090.0056). The association between genetically predicted ABCC8 inhibition and risk of POAG was mainly mediated through intraocular pressure. No association was found for PPARG, SLC5A2, or GLP1R. Sensitivity analyses supported this observation.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>We found a protective effect of genetically proxied ABCC8 inhibition on POAG risk in both Europeans and East Asians, highlighting ABCC8 as a promising candidate drug target for POAG, and mechanisms underlying the protective effect should also be investigated.<\/jats:p><\/jats:sec>","DOI":"10.1002\/hsr2.70162","type":"journal-article","created":{"date-parts":[[2024,10,24]],"date-time":"2024-10-24T08:07:05Z","timestamp":1729757225000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Genetically Proxied Antidiabetic Drug Target and Primary Open\u2010Angle Glaucoma: A Mendelian Randomization Study"],"prefix":"10.1002","volume":"7","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0058-1509","authenticated-orcid":false,"given":"Kefu","family":"Tang","sequence":"first","affiliation":[{"name":"Department of Clinical Laboratory, Prenatal Diagnosis Center, Changning Maternity and Infant Health Hospital East China Normal University Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenqiu","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, Shanghai General Hospital Shanghai Jiao Tong University School of Medicine Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Weiteng","family":"Chang","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, NHC Key Laboratory of Myopia, Shanghai Research Center of Ophthalmology and Optometry, Eye &amp; ENT Hospital Fudan University Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xi","family":"Wu","sequence":"additional","affiliation":[{"name":"Key Laboratory for the Genetics of Developmental and Neuropsychiatric Disorders (Ministry of Education), Bio\u2010X Institutes Shanghai Jiao Tong University Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2024,10,24]]},"reference":[{"key":"e_1_2_14_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ophtha.2014.05.013"},{"key":"e_1_2_14_3_1","doi-asserted-by":"publisher","DOI":"10.1159\/000081775"},{"key":"e_1_2_14_4_1","doi-asserted-by":"publisher","DOI":"10.1076\/ceyr.28.1.47.23487"},{"key":"e_1_2_14_5_1","first-page":"170","article-title":"Effect of High Glucose on Fibronectin Expression and Cell Proliferation in Trabecular Meshwork Cells","volume":"43","author":"Sato T.","year":"2002","journal-title":"Investigative Ophthalmology & Visual 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