{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,19]],"date-time":"2026-10-19T13:46:55Z","timestamp":1792417615031,"version":"4.4.0"},"reference-count":43,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2023,2,23]],"date-time":"2023-02-23T00:00:00Z","timestamp":1677110400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004829","name":"Department of Science and Technology of Sichuan Province","doi-asserted-by":"publisher","award":["2021YFS0051 2023YFS0269 2022NSFSC0749"],"award-info":[{"award-number":["2021YFS0051 2023YFS0269 2022NSFSC0749"]}],"id":[{"id":"10.13039\/501100004829","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81971188"],"award-info":[{"award-number":["81971188"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Pharmacol."],"abstract":"<jats:p><jats:bold>Background:<\/jats:bold> Evidence from observational studies concerning the causal role of blood pressure (BP) and antihypertensive medications (AHM) on Parkinson\u2019s disease (PD) remains inconclusive. A two-sample Mendelian randomization (MR) study was performed to evaluate the unconfounded association of genetic proxies for BP and first-line AHMs with PD.<\/jats:p><jats:p><jats:bold>Methods:<\/jats:bold> Instrumental variables (IV) from the genome-wide association study (GWAS) for BP traits were used to proxy systolic BP (SBP), diastolic BP, and pulse pressure. SBP-associated variants either located within encoding regions or associated with the expression of AHM targets were selected and then scaled to proxy therapeutic inhibition of angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, \u03b2-blockers, calcium channel blockers, and thiazides. Positive control analyses on coronary heart disease (CHD) and stroke were conducted to validate the IV selection. Summary data from GWAS for PD risk and PD age at onset (AAO) were used as outcomes.<\/jats:p><jats:p><jats:bold>Results:<\/jats:bold> In positive control analyses, genetically determined BP traits and AHMs closely mimicked the observed causal effect on CHD and stroke, confirming the validity of IV selection methodology. In primary analyses, although genetic proxies identified by \u201cencoding region-based method\u201d for \u03b2-blockers were suggestively associated with a delayed PD AAO (Beta: 0.115; 95% CI: 0.021, 0.208; <jats:italic>p<\/jats:italic> = 1.63E-2; per 10-mmHg lower), sensitivity analyses failed to support this association. Additionally, MR analyses found little evidence that genetically predicted BP traits, overall AHM, or other AHMs affected PD risk or AAO.<\/jats:p><jats:p><jats:bold>Conclusion:<\/jats:bold> Our data suggest that BP and commonly prescribed AHMs may not have a prominent role in PD etiology.<\/jats:p>","DOI":"10.3389\/fphar.2023.1107248","type":"journal-article","created":{"date-parts":[[2023,2,23]],"date-time":"2023-02-23T05:25:30Z","timestamp":1677129930000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":7,"title":["Protective effect of antihypertensive drugs on the risk of Parkinson\u2019s disease lacks causal evidence from mendelian randomization"],"prefix":"10.3389","volume":"14","author":[{"given":"Zheng","family":"Jiang","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiao-Jing","family":"Gu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei-Ming","family":"Su","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qing-Qing","family":"Duan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yan-Lin","family":"Ren","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ju-Rong","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Li-Yi","family":"Chi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yi","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bei","family":"Cao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yong-Ping","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2023,2,23]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"866","DOI":"10.1002\/mds.27659","article-title":"Parkinson's disease age at onset genome-wide association study: Defining heritability, genetic loci, and alpha-synuclein mechanisms","volume":"34","author":"Blauwendraat","year":"2019","journal-title":"Mov. 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