{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,24]],"date-time":"2026-07-24T20:31:24Z","timestamp":1784925084602,"version":"3.55.0"},"reference-count":40,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2023,9,5]],"date-time":"2023-09-05T00:00:00Z","timestamp":1693872000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Clinical Endocrinology"],"published-print":{"date-parts":[[2024,3]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Objective<\/jats:title><jats:p>Cushing's syndrome is characterized by hypercortisolaemia and is frequently accompanied by comorbidities such as type 2 diabetes, hypertension, osteoporosis, depression and schizophrenia. It is unclear whether moderate but lifelong hypercortisolaemia is causally associated with these diseases in the general population. We aimed to address this research gap using a Mendelian randomization approach.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We used three cortisol\u2010associated genetic variants in the <jats:italic>SERPINA6\/SERPINA1<\/jats:italic> region as genetic instruments in a two\u2010sample, inverse\u2010variance\u2010weighted Mendelian randomization analysis. We obtained summary\u2010level statistics for cortisol and disease outcomes from publicly available genetic consortia, and meta\u2010analysed them as appropriate. We conducted a multivariable Mendelian randomization analysis to assess potential mediating effects.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>A 1\u2009standard deviation higher genetically predicted plasma cortisol was associated with greater odds of hypertension (odds ratio: 1.12; 95% confidence interval [CI]: 1.05\u20131.18) as well as higher systolic blood pressure (mean difference [MD]: 0.03\u2009SD change; 95% CI: 0.01\u20130.05) and diastolic blood pressure (MD: 0.03\u2009SD change; 95% CI: 0.01\u20130.04). There was no evidence of association with type 2 diabetes, osteoporosis, depression and schizophrenia. The association with hypertension was attenuated upon adjustment for waist circumference, suggesting potential mediation through central obesity.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>There is strong evidence for a causal association between plasma cortisol and greater risk for hypertension, potentially mediated by obesity.<\/jats:p><\/jats:sec>","DOI":"10.1111\/cen.14966","type":"journal-article","created":{"date-parts":[[2023,9,5]],"date-time":"2023-09-05T08:25:51Z","timestamp":1693902351000},"page":"238-244","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Genetically predicted plasma cortisol and common chronic diseases: A Mendelian randomization study"],"prefix":"10.1111","volume":"100","author":[{"given":"Wei\u2010Hsuan","family":"Lee","sequence":"first","affiliation":[{"name":"British Heart Foundation, Cardiovascular Epidemiology Unit, Department of Public Health and 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Centre of Research Excellence University of Cambridge Cambridge UK"},{"name":"Health Data Research UK Cambridge Wellcome Genome Campus and University of Cambridge Cambridge UK"},{"name":"Cambridge Centre of Artificial Intelligence in Medicine Cambridge UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emanuele","family":"Di Angelantonio","sequence":"additional","affiliation":[{"name":"British Heart Foundation, Cardiovascular Epidemiology Unit, Department of Public Health and Primary Care University of Cambridge Cambridge UK"},{"name":"Victor Philip Dahdaleh National Institute for Health Research Blood and Transplant Research Unit in Donor Health and Genomics University of Cambridge Cambridge UK"},{"name":"British Heart Foundation Centre of Research Excellence University of Cambridge Cambridge UK"},{"name":"Health Data Research UK Cambridge Wellcome Genome Campus and University of Cambridge Cambridge UK"},{"name":"Health Data Science Research Centre, Human Technopole 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Unit University of Cambridge Cambridge UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1634-8330","authenticated-orcid":false,"given":"Elias","family":"Allara","sequence":"additional","affiliation":[{"name":"British Heart Foundation, Cardiovascular Epidemiology Unit, Department of Public Health and Primary Care University of Cambridge Cambridge UK"},{"name":"Victor Philip Dahdaleh National Institute for Health Research Blood and Transplant Research Unit in Donor Health and Genomics University of Cambridge Cambridge 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