{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,29]],"date-time":"2026-06-29T17:18:47Z","timestamp":1782753527406,"version":"3.54.5"},"reference-count":46,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"15","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["JAHA"],"published-print":{"date-parts":[[2023,8]]},"abstract":"<jats:sec sec-type=\"background\" xml:lang=\"en\">\n            <jats:title>Background<\/jats:title>\n            <jats:p xml:lang=\"en\">Epidemiologic studies have identified risk factors associated with pulmonary hypertension and right heart failure, but causative drivers of pulmonary hypertension and right heart adaptation are not well known. We sought to leverage unbiased genetic approaches to determine clinical conditions that share genetic architecture with pulmonary pressure and right ventricular dysfunction.<\/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 leveraged Vanderbilt University's deidentified electronic health records and DNA biobank to identify 14\u2009861 subjects of European ancestry who underwent at least 1 echocardiogram with available estimates of pulmonary pressure and right ventricular function. Analyses of the study were performed between 2020 and 2022. The final analytical sample included 14\u2009861 participants (mean [SD] age, 63 [15] years and mean [SD] body mass index, 29 [7] kg\/m\n              <jats:sup>2<\/jats:sup>\n              ). An unbiased phenome\u2010wide association study identified diabetes as the most statistically significant clinical\n              <jats:italic>International Classifications of Diseases<\/jats:italic>\n              ,\n              <jats:italic>Ninth Revision<\/jats:italic>\n              (\n              <jats:italic>ICD\u20109<\/jats:italic>\n              ) code associated with polygenic risk for increased pulmonary pressure. We validated this finding further by finding significant associations between genetic risk for diabetes and a related condition, obesity, with pulmonary pressure estimate. We then used 2\u2010sample univariable Mendelian randomization and multivariable Mendelian randomization to show that diabetes, but not obesity, was independently associated with genetic risk for increased pulmonary pressure and decreased right ventricle load stress.\n            <\/jats:p>\n          <\/jats:sec>\n          <jats:sec xml:lang=\"en\">\n            <jats:title>Conclusions<\/jats:title>\n            <jats:p xml:lang=\"en\">Our findings show that genetic risk for diabetes is the only significant independent causative driver of genetic risk for increased pulmonary pressure and decreased right ventricle load stress. These findings suggest that therapies targeting genetic risk for diabetes may also potentially be beneficial in treating pulmonary hypertension and right heart dysfunction.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1161\/jaha.122.029190","type":"journal-article","created":{"date-parts":[[2023,7,31]],"date-time":"2023-07-31T09:17:27Z","timestamp":1690795047000},"update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":11,"title":["Genetics of Pulmonary Pressure and Right Ventricle Stress Identify Diabetes as a Causal Risk Factor"],"prefix":"10.1161","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6093-613X","authenticated-orcid":false,"given":"Minoo","family":"Bagheri","sequence":"first","affiliation":[{"name":"Division of Cardiovascular Medicine, Department of Medicine Vanderbilt University Medical Center Nashville TN USA"},{"name":"Department of Biomedical Informatics Vanderbilt University Medical Center Nashville TN 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