{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,13]],"date-time":"2026-08-13T13:42:45Z","timestamp":1786628565588,"version":"build-2736575974"},"reference-count":38,"publisher":"SAGE Publications","issue":"8","license":[{"start":{"date-parts":[[2026,8,1]],"date-time":"2026-08-01T00:00:00Z","timestamp":1785542400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"},{"start":{"date-parts":[[2026,8,1]],"date-time":"2026-08-01T00:00:00Z","timestamp":1785542400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"funder":[{"name":"Basic Research Fund of Naval Medical University","award":["2024MS006"],"award-info":[{"award-number":["2024MS006"]}]},{"DOI":"10.13039\/100007219","name":"Shanghai Natural Science Foundation","doi-asserted-by":"crossref","award":["25ZR1402584"],"award-info":[{"award-number":["25ZR1402584"]}],"id":[{"id":"10.13039\/100007219","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["J Int Med Res"],"published-print":{"date-parts":[[2026,8]]},"abstract":"<jats:sec>\n                    <jats:title>Objectives<\/jats:title>\n                    <jats:p>Circadian rhythms regulate human health, and observational studies have linked their disruption to hypertension; however, confounding factors and reverse causality limit causal interpretation. We aimed to evaluate the existing evidence linking circadian gene sets and hypertension using Mendelian randomization.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      Two-sample Mendelian randomization was performed using genome-wide association study summary-level data from non-overlapping European ancestry samples. Genetic variants of 1276 circadian genes (\n                      <jats:italic toggle=\"yes\">CGDB<\/jats:italic>\n                      ) were instrumental variables; the outcome was hypertension genome-wide association study data from the UK Biobank (ieu-b-5144; 463,010 participants). Single nucleotide polymorphisms were selected at\n                      <jats:italic toggle=\"yes\">p<\/jats:italic>\n                      &lt;5\u2009\u00d7\u200910\n                      <jats:sup>\u22128<\/jats:sup>\n                      (mean F-statistic: 276.5). Inverse variance weighting was the primary method used. Benjamini\u2013Hochberg false discovery rate correction was applied across all 1276 genes. Sensitivity analyses were performed using heterogeneity testing, Mendelian randomization\u2013Egger regression, Mendelian Randomization Pleiotropy RESidual Sum and Outlier, Steiger directionality testing, and leave-one-out analyses.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Mendelian randomization identified 39 nominally significant associations (inverse variance weighting,\n                      <jats:italic toggle=\"yes\">p<\/jats:italic>\n                      \u2009&lt;\u20090.05). After false discovery rate correction, four genes reached statistical significance:\n                      <jats:italic toggle=\"yes\">PHOSPHO1<\/jats:italic>\n                      (odds ratio\u2009=\u20090.988, 95% confidence interval: 0.983\u20130.993),\n                      <jats:italic toggle=\"yes\">BAIAP3<\/jats:italic>\n                      (odds ratio\u2009=\u20091.009, 95% confidence interval: 1.005\u20131.014),\n                      <jats:italic toggle=\"yes\">OSGIN2<\/jats:italic>\n                      (odds ratio\u2009=\u20090.990, 95% confidence interval: 0.986\u20130.995), and\n                      <jats:italic toggle=\"yes\">ZDHHC18<\/jats:italic>\n                      (odds ratio\u2009=\u20091.012, 95% confidence interval: 1.007\u20131.018). The remaining nominal associations did not survive false discovery rate correction and were classified as exploratory. Functional enrichment implicated circadian rhythm, apoptosis, and glycosaminoglycan biosynthesis pathways. Sensitivity analyses did not reveal significant heterogeneity or pleiotropy.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>\n                      These findings are hypothesis-generating and require experimental validation.\n                      <jats:italic toggle=\"yes\">PHOSPHO1<\/jats:italic>\n                      ,\n                      <jats:italic toggle=\"yes\">BAIAP3<\/jats:italic>\n                      ,\n                      <jats:italic toggle=\"yes\">OSGIN2<\/jats:italic>\n                      , and\n                      <jats:italic toggle=\"yes\">ZDHHC18<\/jats:italic>\n                      demonstrated statistically significant associations with hypertension risk after false discovery rate correction and should be prioritized for follow-up. Other nominal findings should be interpreted as exploratory.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1177\/03000605261474730","type":"journal-article","created":{"date-parts":[[2026,8,11]],"date-time":"2026-08-11T14:56:34Z","timestamp":1786460194000},"update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":0,"title":["Genetic evidence linking circadian rhythm genes and hypertension: A two-sample Mendelian randomization study"],"prefix":"10.1177","volume":"54","author":[{"ORCID":"https:\/\/orcid.org\/0009-0003-0799-5944","authenticated-orcid":false,"given":"Lu-Jie","family":"Wang","sequence":"first","affiliation":[{"name":"Shanghai University"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yue-Qi","family":"Leng","sequence":"additional","affiliation":[{"name":"Naval Medical University"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei-Zhong","family":"Wang","sequence":"additional","affiliation":[{"name":"Shanghai University"},{"name":"Naval Medical University"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jia-Cen","family":"Sun","sequence":"additional","affiliation":[{"name":"Naval Medical University"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"179","published-online":{"date-parts":[[2026,8,11]]},"reference":[{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature10405"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(05)17741-1"},{"key":"e_1_3_3_4_2","article-title":"A genome-wide linkage and association scan reveals novel loci for hypertension and blood pressure traits","volume":"7","author":"Guo Y","year":"2012","unstructured":"Guo Y, Tomlinson B, Chu T, et al. 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