{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,4]],"date-time":"2026-08-04T07:10:07Z","timestamp":1785827407832,"version":"3.56.0"},"reference-count":48,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"6","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Circ: Genomic and Precision Medicine"],"published-print":{"date-parts":[[2020,12]]},"abstract":"<jats:sec>\n                    <jats:title>Background:<\/jats:title>\n                    <jats:p>The aortic valve is an important determinant of cardiovascular physiology and anatomic location of common human diseases.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods:<\/jats:title>\n                    <jats:p>From a sample of 34\u2009287 white British ancestry participants, we estimated functional aortic valve area by planimetry from prospectively obtained cardiac magnetic resonance imaging sequences of the aortic valve. Aortic valve area measurements were submitted to genome-wide association testing, followed by polygenic risk scoring and phenome-wide screening, to identify genetic comorbidities.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results:<\/jats:title>\n                    <jats:p>\n                      A genome-wide association study of aortic valve area in these UK Biobank participants showed 3 significant associations, indexed by rs71190365 (chr13:50764607,\n                      <jats:italic>DLEU1<\/jats:italic>\n                      ,\n                      <jats:italic>P<\/jats:italic>\n                      =1.8\u00d710\n                      <jats:sup>\u22129<\/jats:sup>\n                      ), rs35991305 (chr12:94191968,\n                      <jats:italic>CRADD<\/jats:italic>\n                      ,\n                      <jats:italic>P<\/jats:italic>\n                      =3.4\u00d710\n                      <jats:sup>\u22128<\/jats:sup>\n                      ), and chr17:45013271:C:T (\n                      <jats:italic>GOSR2<\/jats:italic>\n                      ,\n                      <jats:italic>P<\/jats:italic>\n                      =5.6\u00d710\n                      <jats:sup>\u22128<\/jats:sup>\n                      ). Replication on an independent set of 8145 unrelated European ancestry participants showed consistent effect sizes in all 3 loci, although rs35991305 did not meet nominal significance. We constructed a polygenic risk score for aortic valve area, which in a separate cohort of 311\u2009728 individuals without imaging demonstrated that smaller aortic valve area is predictive of increased risk for aortic valve disease (odds ratio, 1.14;\n                      <jats:italic>P<\/jats:italic>\n                      =2.3\u00d710\n                      <jats:sup>\u22126<\/jats:sup>\n                      ). After excluding subjects with a medical diagnosis of aortic valve stenosis (remaining n=308\u2009683 individuals), phenome-wide association of &gt;10\u2009000 traits showed multiple links between the polygenic score for aortic valve disease and key health-related comorbidities involving the cardiovascular system and autoimmune disease. Genetic correlation analysis supports a shared genetic etiology with between aortic valve area and birth weight along with other cardiovascular conditions.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions:<\/jats:title>\n                    <jats:p>These results illustrate the use of automated phenotyping of cardiac imaging data from the general population to investigate the genetic etiology of aortic valve disease, perform clinical prediction, and uncover new clinical and genetic correlates of cardiac anatomy.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1161\/circgen.120.003014","type":"journal-article","created":{"date-parts":[[2020,10,30]],"date-time":"2020-10-30T12:01:11Z","timestamp":1604059271000},"source":"Crossref","is-referenced-by-count":26,"title":["Cardiac Imaging of Aortic Valve Area From 34 287 UK Biobank Participants Reveals Novel Genetic Associations and Shared Genetic Comorbidity With Multiple Disease Phenotypes"],"prefix":"10.1161","volume":"13","author":[{"given":"Aldo","family":"C\u00f3rdova-Palomera","sequence":"first","affiliation":[{"name":"Department of Pediatrics, Division of Pediatric Cardiology, Stanford University School of Medicine, Stanford, CA (A.C.-P., C.T., K.X., H.T., J.R.P.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9559-4339","authenticated-orcid":true,"given":"Catherine","family":"Tcheandjieu","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Division of Pediatric Cardiology, Stanford University School of Medicine, Stanford, CA (A.C.-P., C.T., K.X., H.T., J.R.P.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9316-5768","authenticated-orcid":true,"given":"Jason A.","family":"Fries","sequence":"additional","affiliation":[{"name":"Department of Computer Science (J.F., V.S.C., M.F., C.R.), Stanford University, CA."},{"name":"Center for Biomedical Informatics Research (J.F.), Stanford University, CA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paroma","family":"Varma","sequence":"additional","affiliation":[{"name":"Department of Electrical Engineering (P.V.), Stanford University, CA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1320-120X","authenticated-orcid":true,"given":"Vincent S.","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Computer Science (J.F., V.S.C., M.F., C.R.), Stanford University, CA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4179-7274","authenticated-orcid":true,"given":"Madalina","family":"Fiterau","sequence":"additional","affiliation":[{"name":"Department of Computer Science (J.F., V.S.C., M.F., C.R.), Stanford University, CA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6453-0420","authenticated-orcid":true,"given":"Ke","family":"Xiao","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Division of Pediatric Cardiology, Stanford University School of Medicine, Stanford, CA (A.C.-P., C.T., K.X., H.T., J.R.P.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6726-4658","authenticated-orcid":true,"given":"Heliodoro","family":"Tejeda","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Division of Pediatric Cardiology, Stanford University School of Medicine, Stanford, CA (A.C.-P., C.T., K.X., H.T., J.R.P.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9573-0812","authenticated-orcid":true,"given":"Bernard D.","family":"Keavney","sequence":"additional","affiliation":[{"name":"Division of Cardiovascular Sciences, Faculty of Biology, Medicine and Health, The University of Manchester, Manchester, United Kingdom (B.K.)."},{"name":"Division of Medicine, Manchester University National Health Service Foundation Trust, Manchester Academic Health Science Centre, Manchester, United Kingdom (B.K.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1879-5572","authenticated-orcid":true,"given":"Heather J.","family":"Cordell","sequence":"additional","affiliation":[{"name":"Population Health Sciences Institute, Faculty of Medical Sciences, Newcastle University, Newcastle Upon Tyne, United Kingdom (H.J.C.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9759-157X","authenticated-orcid":true,"given":"Yosuke","family":"Tanigawa","sequence":"additional","affiliation":[{"name":"Department of Biomedical Data Science (Y.T., G.V., M.R.), Stanford University, CA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0754-6631","authenticated-orcid":true,"given":"Guhan","family":"Venkataraman","sequence":"additional","affiliation":[{"name":"Department of Biomedical Data Science (Y.T., G.V., M.R.), Stanford University, CA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Manuel A.","family":"Rivas","sequence":"additional","affiliation":[{"name":"Department of Biomedical Data Science (Y.T., G.V., M.R.), Stanford University, CA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christopher","family":"R\u00e9","sequence":"additional","affiliation":[{"name":"Department of Computer Science (J.F., V.S.C., M.F., C.R.), Stanford University, CA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Euan","family":"Ashley","sequence":"additional","affiliation":[{"name":"Department of Medicine (E.A.), Stanford University, CA."},{"name":"Chan Zuckerberg Biohub, San 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