{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,13]],"date-time":"2026-05-13T18:12:18Z","timestamp":1778695938027,"version":"3.51.4"},"reference-count":20,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"9","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["JAHA"],"published-print":{"date-parts":[[2024,5,7]]},"abstract":"<jats:sec sec-type=\"background\" xml:lang=\"en\">\n            <jats:title>Background<\/jats:title>\n            <jats:p xml:lang=\"en\">Large observational studies have demonstrated a clear inverse association between renal function and risk of aortic stenosis (AS). Whether this represents a causal, reverse causal or correlative relationship remains unclear. We investigated this using a bidirectional 2\u2010sample Mendelian randomization approach.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec xml:lang=\"en\">\n            <jats:title>Methods and Results<\/jats:title>\n            <jats:p xml:lang=\"en\">\n              We collected summary statistics for the primary analysis of chronic kidney disease (CKD) and AS from genome\u2010wide association study meta\u2010analyses including 480\u2009698 and 653\u2009867 participants, respectively. We collected further genome\u2010wide association study summary statistics from up to 1\u2009004\u2009040 participants for sensitivity analyses involving estimated glomerular filtration rate (eGFR) derived from creatinine, eGFR derived from cystatin C, and serum urea nitrogen. Inverse\u2010variance weighted was the primary analysis method, with weighted\u2010median, weighted\u2010mode, Mendelian randomization\u2010Egger, and Mendelian randomization\u2010Pleiotropy Residual Sum and Outlier as sensitivity analyses. We did not find evidence of a causal relationship between genetically predicted CKD liability as the exposure and AS as the outcome (odds ratio [OR], 0.94 per unit increase in log odds of genetic liability to CKD [95% CI, 0.85\u20131.04],\n              <jats:italic>P<\/jats:italic>\n              =0.26) nor robust evidence of AS liability as the exposure and CKD as the outcome (OR, 1.04 per unit increase in log odds of genetic liability to AS [95% CI, 0.97\u20131.12],\n              <jats:italic>P<\/jats:italic>\n              =0.30). The sensitivity analyses were neutral overall, as were the analyses using eGFR derived from creatinine, eGFR derived from cystatin C, and serum urea nitrogen. All positive controls demonstrated strong significant associations.\n            <\/jats:p>\n          <\/jats:sec>\n          <jats:sec xml:lang=\"en\">\n            <jats:title>Conclusions<\/jats:title>\n            <jats:p xml:lang=\"en\">The present study did not find evidence of a substantial effect of genetically predicted renal impairment on risk of AS. This has important implications for research efforts that attempt to identify prevention and treatment targets for both CKD and AS.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1161\/jaha.123.034102","type":"journal-article","created":{"date-parts":[[2024,4,19]],"date-time":"2024-04-19T11:09:56Z","timestamp":1713524996000},"update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":8,"title":["Aortic Stenosis and Renal Function: A Bidirectional Mendelian Randomization Analysis"],"prefix":"10.1161","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4476-6051","authenticated-orcid":false,"given":"Jonathan L.","family":"Ciofani","sequence":"first","affiliation":[{"name":"Faculty of Medicine and Health The University of Sydney Sydney NSW Australia"},{"name":"Department of Cardiology Royal North Shore Hospital Sydney NSW Australia"},{"name":"Department of Epidemiology and Biostatistics, School of Public Health Imperial College London London UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9088-1651","authenticated-orcid":false,"given":"Daniel","family":"Han","sequence":"additional","affiliation":[{"name":"Medical Research Council Laboratory of Molecular Biology Cambridge UK"},{"name":"Department of Physiology, Development and Neuroscience University of Cambridge Cambridge UK"},{"name":"School of Mathematics and Statistics University of New South Wales Sydney NSW Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7178-4744","authenticated-orcid":false,"given":"Usaid K.","family":"Allahwala","sequence":"additional","affiliation":[{"name":"Faculty of Medicine and Health The University of Sydney Sydney NSW Australia"},{"name":"Department of Cardiology Royal North Shore Hospital Sydney NSW 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