{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,26]],"date-time":"2026-08-26T05:20:12Z","timestamp":1787721612908,"version":"build-2784847793"},"reference-count":67,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"13","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["JAHA"],"published-print":{"date-parts":[[2026,7,7]]},"abstract":"<jats:sec xml:lang=\"en\">\n                    <jats:title>Background<\/jats:title>\n                    <jats:p xml:lang=\"en\">\n                      High plasma lipoprotein (a) (Lp[a]) levels, largely regulated by variation in the\n                      <jats:italic toggle=\"no\">LPA<\/jats:italic>\n                      gene, are a causal risk factor for atherosclerotic cardiovascular disease.\n                      <jats:italic toggle=\"no\">LPA<\/jats:italic>\n                      Kringle IV type 2 (KIV\u20102) copy number (CN) inversely associates with Lp(a) levels, with Black and Hispanic individuals exhibiting higher Lp(a) levels than White individuals. These populations are underrepresented in genetic studies. We evaluated the ancestry\u2010specific\n                      <jats:italic toggle=\"no\">LPA<\/jats:italic>\n                      KIV\u20102 variants and their associations with cardiometabolic and neurologic traits.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec xml:lang=\"en\">\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p xml:lang=\"en\">\n                      Whole\u2010exome sequencing data from 3817 participants in the Washington Heights Inwood Columbia Aging Project were analyzed, including 886 non\u2010Hispanic White individuals (23%), 1811 Caribbean Hispanic individuals (47%), and 1120 Black individuals (29%).\n                      <jats:italic toggle=\"no\">LPA<\/jats:italic>\n                      KIV\u20102 CN estimation and variant calling were performed using validated pipelines. Associations with clinical outcomes were evaluated using regression models adjusted for age, sex, and population substructure.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec xml:lang=\"en\">\n                    <jats:title>Results<\/jats:title>\n                    <jats:p xml:lang=\"en\">\n                      A total of 1421 variants were identified in the\n                      <jats:italic toggle=\"no\">LPA<\/jats:italic>\n                      KIV\u20102 region, including 267 exonic variants, 35% shared across ancestry groups.\n                      <jats:italic toggle=\"no\">LPA<\/jats:italic>\n                      KIV\u20102 CN correlated with 314 variants, 65.6% associated with lower KIV\u20102 CN and higher Lp(a) levels. Three novel exonic variants (4785\u2010C\/A, 727\u2010T\/C, and 723\u2010A\/G) positively associated with hypertension across ancestry groups. Variant 412\u2010C\/T was associated to lower glucose levels, independently of KIV\u20102 CN; 4785\u2010C\/A was negatively associated with KIV\u2010CN (\n                      <jats:italic toggle=\"no\">P<\/jats:italic>\n                      =2.3e\u2010159) and hypertension (\n                      <jats:italic toggle=\"no\">P<\/jats:italic>\n                      =0.032); and in a small cohort, it was negatively associated with weighted isoform size (\n                      <jats:italic toggle=\"no\">P<\/jats:italic>\n                      =1.5e\u20104) and positively associated with Lp(a) levels (\n                      <jats:italic toggle=\"no\">P<\/jats:italic>\n                      =0.012).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec xml:lang=\"en\">\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p xml:lang=\"en\">\n                      Novel\n                      <jats:italic toggle=\"no\">LPA<\/jats:italic>\n                      KIV\u20102 variants are enriched in individuals with low KIV\u20102 CN and are associated with hypertension and glucose levels. These findings support further investigation into Lp(a)\u2010mediated mechanisms underlying atherosclerotic cardiovascular disease.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1161\/jaha.125.043246","type":"journal-article","created":{"date-parts":[[2026,6,23]],"date-time":"2026-06-23T10:35:18Z","timestamp":1782210918000},"update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":0,"title":["<i>LPA<\/i>\n                    Kringle IV Type\u20102 Genetic Variants Are Associated With Apolipoprotein (a) Size, Hypertension, and Nonfasting Glucose Levels"],"prefix":"10.1161","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0009-0009-8722-3437","authenticated-orcid":false,"given":"Yihao","family":"Li","sequence":"first","affiliation":[{"name":"Columbia University Vagelos College of Physicians and Surgeons","place":["New York"]},{"name":"Columbia University Vagelos College of Physicians and Surgeons","place":["New York"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2229-1120","authenticated-orcid":false,"given":"Florian","family":"Kronenberg","sequence":"additional","affiliation":[{"name":"Medical University of Innsbruck","place":["Innsbruck, Austria"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5677-8979","authenticated-orcid":false,"given":"Stefan","family":"Coassin","sequence":"additional","affiliation":[{"name":"Medical University of Innsbruck","place":["Innsbruck, Austria"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5560-4085","authenticated-orcid":false,"given":"Badri","family":"Vardarajan","sequence":"additional","affiliation":[{"name":"Columbia University Vagelos College of Physicians and Surgeons","place":["New York"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6746-4569","authenticated-orcid":false,"given":"Gissette","family":"Reyes\u2010Soffer","sequence":"additional","affiliation":[{"name":"Columbia University Vagelos College of Physicians and Surgeons","place":["New 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