{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,21]],"date-time":"2026-06-21T18:47:41Z","timestamp":1782067661731,"version":"3.54.5"},"reference-count":34,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"3","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["Circ: Genomic and Precision Medicine"],"published-print":{"date-parts":[[2026,6]]},"abstract":"<jats:sec>\n                    <jats:title>BACKGROUND:<\/jats:title>\n                    <jats:p>Lymphedema is a chronic condition characterized by the accumulation of fluid due to impaired lymphatic drainage, frequently occurring secondary to chronic venous insufficiency (CVI), malignancy, or obesity. Despite known environmental and clinical risk factors, the genetic contributors to lymphedema and CVI have been understudied.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>METHODS:<\/jats:title>\n                    <jats:p>We conducted a multipopulation genome-wide association study in participants of the Million Veteran Program without cancer to identify genetic variants associated with CVI, lymphedema, and their cooccurrence. Individuals were categorized into 3 case groups: CVI only (n=34\u2009664), lymphedema only (n=2452), and lymphedema+CVI (n=3283) and were compared with 367\u2009684 controls.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>RESULTS:<\/jats:title>\n                    <jats:p>\n                      We identified 11 genome-wide significant variants (\n                      <jats:italic toggle=\"yes\">P<\/jats:italic>\n                      &lt;5\u00d710\n                      <jats:sup>\u22128<\/jats:sup>\n                      ) in the multipopulation analysis, including 8 for CVI only, 1 for lymphedema only, and 2 for lymphedema+CVI, and 2 population-specific genetic variants. Three independent variants replicated in the UK Biobank for CVI only near\n                      <jats:italic toggle=\"yes\">CASZ1<\/jats:italic>\n                      ,\n                      <jats:italic toggle=\"yes\">SLC12A2<\/jats:italic>\n                      , and\n                      <jats:italic toggle=\"yes\">NDP<\/jats:italic>\n                      . Polygenic risk scores derived from the Million Veteran Program were associated with CVI in the UK Biobank and phenome-wide associations of CVI-associated variants revealed pleiotropic associations with cardiometabolic traits.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>CONCLUSIONS:<\/jats:title>\n                    <jats:p>These findings enhance our understanding of the genetic architecture of lymphatic dysfunction.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1161\/circgen.125.005442","type":"journal-article","created":{"date-parts":[[2026,4,22]],"date-time":"2026-04-22T09:00:39Z","timestamp":1776848439000},"update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":0,"title":["Genome-Wide Association Study of Chronic Venous Insufficiency and Lymphedema in the Million Veteran Program"],"prefix":"10.1161","volume":"19","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5355-8636","authenticated-orcid":true,"given":"Gina M.","family":"Peloso","sequence":"first","affiliation":[{"name":"Division of Population Health and Data Sciences, Massachusetts Veterans Epidemiology Research and Information Collaborative, VA Boston Healthcare System, MA (G.M.P., N.A., M.M.Y., K.C.)."},{"name":"Department of Biostatistics, Boston University School of Public Health, MA (G.M.P., N.A.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-8810-7957","authenticated-orcid":true,"given":"Nimish","family":"Adhikari","sequence":"additional","affiliation":[{"name":"Division of Population Health and Data Sciences, Massachusetts Veterans Epidemiology Research and Information Collaborative, VA Boston Healthcare System, MA (G.M.P., N.A., M.M.Y., K.C.)."},{"name":"Department of Biostatistics, Boston University School of Public Health, MA (G.M.P., N.A.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3836-9677","authenticated-orcid":true,"given":"Melissa M.","family":"Young","sequence":"additional","affiliation":[{"name":"Division of Population Health and Data Sciences, Massachusetts Veterans Epidemiology Research and Information Collaborative, VA Boston Healthcare System, MA (G.M.P., N.A., M.M.Y., K.C.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1727-7076","authenticated-orcid":true,"given":"Kelly","family":"Cho","sequence":"additional","affiliation":[{"name":"Division of Population Health and Data Sciences, Massachusetts Veterans Epidemiology Research and Information Collaborative, VA Boston Healthcare System, MA (G.M.P., N.A., M.M.Y., K.C.)."},{"name":"Harvard Medical School, Boston, MA (K.C., S.K.)."},{"name":"Massachusetts General Brigham Hospital, Boston (K.C., S.K.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7687-9136","authenticated-orcid":true,"given":"Scott","family":"Kinlay","sequence":"additional","affiliation":[{"name":"VA Boston Healthcare System, West Roxbury, MA (S.K.)."},{"name":"Harvard Medical School, Boston, MA (K.C., S.K.)."},{"name":"Massachusetts General Brigham Hospital, Boston (K.C., S.K.)."},{"name":"Boston University Chobanian and Avedisian School of Medicine, MA (S.K.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sumitra","family":"Muralidhar","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jennifer","family":"Moser","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jennifer E.","family":"Deen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Philip S.","family":"Tsao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sumitra","family":"Muralidhar","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J. 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