{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,28]],"date-time":"2026-05-28T05:07:52Z","timestamp":1779944872640,"version":"3.53.1"},"reference-count":30,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"4","license":[{"start":{"date-parts":[[2026,3,20]],"date-time":"2026-03-20T00:00:00Z","timestamp":1773964800000},"content-version":"unspecified","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":["lww.com","ovid.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2026,7]]},"abstract":"\n Purpose<\/jats:title>\n Valsartan, an angiotensin II receptor blocker, is widely used for hypertension and heart failure. While its cardiovascular benefits are established, its broader pharmacological effects remain incompletely characterized. This study aimed to identify genetic variants associated with valsartan use and to systematically explore its potential effects and adverse events across a wide range of phenotypes.<\/jats:p>\n <\/jats:sec>\n \n Methods<\/jats:title>\n Using UK Biobank data, we selected participants of European ancestry prescribed valsartan as cases, compared with controls not prescribed any ARBs. A genome-wide association study (GWAS) was conducted to identify suggestive genetic variants associated with valsartan use. These variants were then used as instruments in a phenome-wide association study (PheWAS) to screen for associated traits. Mendelian randomization analyses, including inverse-variance weighted and pleiotropy-robust methods, were employed to assess potential causal relationships.<\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n \n The GWAS identified 19 suggestive single nucleotide polymorphisms (\n P<\/jats:italic>\n \u2005<\u20051\u2005\u00d7\u200510\n \u22125<\/jats:sup>\n ) near genes, including\n PREP<\/jats:italic>\n ,\n GCLC<\/jats:italic>\n , and\n ZNF133<\/jats:italic>\n . The PheWAS analysis revealed associations with 14 phenotypes, including lower levels of total cholesterol (\n \u03b2<\/jats:italic>\n = \u22120.59) and low-density lipoprotein cholesterol (LDL-C) (\n \u03b2<\/jats:italic>\n = \u22120.56), and increased risk of cough (odds ratio\u2005=\u20051.67). Mendelian randomization provided genetic evidence consistent with potential causal effects of valsartan in lowering LDL-C (\n \u03b2<\/jats:italic>\n = \u22122.34\u2005\u00d7\u200510\n \u22123<\/jats:sup>\n ) and reducing the risk of transient cerebral ischemic attack.\n <\/jats:p>\n <\/jats:sec>\n \n Conclusion<\/jats:title>\n Our genetic-based study suggests valsartan use may be associated with lowered LDL-C and reduced risks of certain ischemic cardiovascular events. These findings generate novel hypotheses regarding the drug\u2019s pleiotropic effects and potential applications beyond hypertension management, which warrant further clinical investigation.<\/jats:p>\n <\/jats:sec>","DOI":"10.1097\/fpc.0000000000000597","type":"journal-article","created":{"date-parts":[[2026,3,20]],"date-time":"2026-03-20T20:00:15Z","timestamp":1774036815000},"page":"134-142","update-policy":"https:\/\/doi.org\/10.1097\/lww.0000000000001000","source":"Crossref","is-referenced-by-count":0,"title":["The potential effect and pathway of valsartan: genome-wide and phenome-wide association study from UK Biobank data"],"prefix":"10.1097","volume":"36","author":[{"given":"Shengyin","family":"Zeng","sequence":"first","affiliation":[{"name":"College of Life Sciences, University of Chinese Academy of Sciences, Beijing"},{"name":"BGI Genomics, Shenzhen"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yaxin","family":"Li","sequence":"additional","affiliation":[{"name":"College of Life Sciences, University of Chinese Academy of Sciences, Beijing"},{"name":"BGI Genomics, Shenzhen"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yucong","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Geriatrics, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yueqi","family":"Lu","sequence":"additional","affiliation":[{"name":"BGI Genomics, Shenzhen"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lei","family":"Ruan","sequence":"additional","affiliation":[{"name":"Department of Geriatrics, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cuntai","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Geriatrics, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jianguo","family":"Zhang","sequence":"additional","affiliation":[{"name":"BGI Genomics, Shenzhen"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bangwei","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Geriatrics, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology"},{"name":"Key Laboratory of Vascular Aging, Ministry of Education, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tao","family":"Li","sequence":"additional","affiliation":[{"name":"BGI Genomics, Shenzhen"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","published-online":{"date-parts":[[2026,3,20]]},"reference":[{"key":"R1-20260528","doi-asserted-by":"crossref","first-page":"2982","DOI":"10.1016\/j.jacc.2020.11.010","article-title":"Global burden of cardiovascular diseases and risk factors, 1990-2019: update from the GBD 2019 study.","volume":"76","author":"Roth","year":"2020","journal-title":"J Am Coll Cardiol"},{"key":"R2-20260528","doi-asserted-by":"crossref","first-page":"1487","DOI":"10.1161\/HYPERTENSIONAHA.122.19256","article-title":"Hypertension, arterial stiffness, and diabetes: a prospective cohort study.","volume":"79","author":"Tian","year":"2022","journal-title":"Hypertension"},{"key":"R3-20260528","doi-asserted-by":"crossref","first-page":"104619","DOI":"10.1016\/j.ebiom.2023.104619","article-title":"Global distributions of age- and sex-related arterial stiffness: systematic review and meta-analysis of 167 studies with 509,743 participants.","volume":"92","author":"Lu","year":"2023","journal-title":"EBioMedicine"},{"key":"R4-20260528","doi-asserted-by":"crossref","first-page":"545","DOI":"10.1161\/CIRCRESAHA.122.320796","article-title":"Arterial stiffness and diabetes risk in framingham heart study and UK biobank.","volume":"131","author":"Cohen","year":"2022","journal-title":"Circ Res"},{"key":"R5-20260528","doi-asserted-by":"crossref","first-page":"657","DOI":"10.1080\/10641963.2018.1529781","article-title":"Angiotensin II type 1 receptor blockers prevent aortic arterial stiffness in elderly patients with hypertension.","volume":"41","author":"Zhu","year":"2019","journal-title":"Clin Exp Hypertens"},{"key":"R6-20260528","doi-asserted-by":"crossref","first-page":"1225795","DOI":"10.3389\/fphar.2023.1225795","article-title":"Comparative effect of antihypertensive drugs in improving arterial stiffness in adults with hypertension (RIGIPREV study). 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