{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,3]],"date-time":"2026-09-03T14:05:58Z","timestamp":1788444358884,"version":"build-2803163510"},"reference-count":28,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"5","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["Circ: Genomic and Precision Medicine"],"published-print":{"date-parts":[[2024,10]]},"abstract":"<jats:sec>\n            <jats:title>BACKGROUND:<\/jats:title>\n            <jats:p>Coronary atherosclerotic burden and adverse coronary heart disease events are related phenotypes with likely shared genetic cause.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>METHODS:<\/jats:title>\n            <jats:p>\n              We analyzed 6021 patients with available coronary angiography, genotyping, and exome sequencing data. We tested for associations of polygenic risk scores for coronary heart disease (PRS\n              <jats:sub>CHD<\/jats:sub>\n              ) with multiple measures of coronary artery disease (CAD) severity. We assessed the joint associations of PRS\n              <jats:sub>CHD<\/jats:sub>\n              and pathogenic\/likely pathogenic variants in 3 familial hypercholesterolemia genes, with CAD severity. We performed mediation analyses to explore whether CAD severity mediated the association of PRS\n              <jats:sub>CHD<\/jats:sub>\n              with prevalent coronary heart disease and incident myocardial infarction.\n            <\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>RESULTS:<\/jats:title>\n            <jats:p>\n              A 1-SD increase in PRS\n              <jats:sub>CHD<\/jats:sub>\n              was associated with multiple measures of CAD severity, including the log Gensini score (\u03b2, 0.31 [95% CI, 0.28\u20130.33]). Carrying a pathogenic\/likely pathogenic familial hypercholesterolemia variant was associated with a higher log Gensini score after adjustment for PRS\n              <jats:sub>CHD<\/jats:sub>\n              (\u03b2, 0.21 [95% CI, 0.03\u20130.38]). A 1-SD increase in PRS\n              <jats:sub>CHD<\/jats:sub>\n              was associated with incident myocardial infarction over a mean follow-up of 9.2 years (hazard ratio, 1.20 [95% CI, 1.13\u20131.27];\n              <jats:italic toggle=\"yes\">P<\/jats:italic>\n              =5\u00d710\n              <jats:sup>\u2212<\/jats:sup>\n              <jats:sup>10<\/jats:sup>\n              ), and the Gensini score mediated 90% of this association.\n            <\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>CONCLUSIONS:<\/jats:title>\n            <jats:p>\n              PRS\n              <jats:sub>CHD<\/jats:sub>\n              was associated with multiple measures of CAD severity. The association of PRS\n              <jats:sub>CHD<\/jats:sub>\n              with incident myocardial infarction was almost fully mediated by CAD severity, indicating a considerable genetic overlap between the 2 phenotypes.\n            <\/jats:p>\n          <\/jats:sec>","DOI":"10.1161\/circgen.123.004470","type":"journal-article","created":{"date-parts":[[2024,8,8]],"date-time":"2024-08-08T09:00:39Z","timestamp":1723107639000},"update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":7,"title":["Polygenic Risk and Coronary Artery Disease Severity"],"prefix":"10.1161","volume":"17","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8394-0919","authenticated-orcid":true,"given":"Alborz","family":"Sherafati","sequence":"first","affiliation":[{"name":"Department of Cardiovascular Medicine (A.S., K.N., M.N., I.J.K.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0009-3418-119X","authenticated-orcid":true,"given":"Kristjan","family":"Norland","sequence":"additional","affiliation":[{"name":"Department of Cardiovascular Medicine (A.S., K.N., M.N., I.J.K.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1827-3173","authenticated-orcid":true,"given":"Mohammadreza","family":"Naderian","sequence":"additional","affiliation":[{"name":"Department of Cardiovascular Medicine (A.S., K.N., M.N., I.J.K.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1457-6433","authenticated-orcid":true,"given":"Daniel J.","family":"Schaid","sequence":"additional","affiliation":[{"name":"Department of Health Sciences Research (D.J.S.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6524-3471","authenticated-orcid":true,"given":"Iftikhar J.","family":"Kullo","sequence":"additional","affiliation":[{"name":"Department of Cardiovascular Medicine (A.S., K.N., M.N., I.J.K.)."},{"name":"Gonda Vascular Center, Mayo Clinic, Rochester, MN (I.J.K.)."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","reference":[{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-017-03062-8"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1038\/ng.3874"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCRESAHA.117.312086"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41588-022-01233-6"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41591-022-01891-3"},{"key":"e_1_3_3_7_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.115.020109"},{"key":"e_1_3_3_8_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41588-018-0183-z"},{"key":"e_1_3_3_9_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCRESAHA.120.315928"},{"key":"e_1_3_3_10_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41591-023-02429-x"},{"key":"e_1_3_3_11_2","doi-asserted-by":"publisher","DOI":"10.1038\/sj.ejhg.5201854"},{"key":"e_1_3_3_12_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCGENETICS.108.793158"},{"key":"e_1_3_3_13_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(10)61996-4"},{"key":"e_1_3_3_14_2","doi-asserted-by":"publisher","DOI":"10.7326\/0003-4819-129-12-199812150-00010"},{"key":"e_1_3_3_15_2","doi-asserted-by":"publisher","DOI":"10.1161\/ATVBAHA.114.304985"},{"key":"e_1_3_3_16_2","doi-asserted-by":"publisher","DOI":"10.1161\/ATVBAHA.115.306944"},{"key":"e_1_3_3_17_2","doi-asserted-by":"publisher","DOI":"10.1186\/s12933-020-0988-9"},{"key":"e_1_3_3_18_2","doi-asserted-by":"publisher","DOI":"10.1161\/JAHA.119.014795"},{"key":"e_1_3_3_19_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-020-17374-3"},{"key":"e_1_3_3_20_2","doi-asserted-by":"publisher","DOI":"10.1093\/eurheartj\/ehaa1040"},{"key":"e_1_3_3_21_2","unstructured":"UK Biobank. Neale lab. Accessed March 18 2024. http:\/\/www.nealelab.is\/uk-biobank"},{"key":"e_1_3_3_22_2","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddaa052"},{"key":"e_1_3_3_23_2","doi-asserted-by":"publisher","DOI":"10.1136\/bmjopen-2019-032707"},{"key":"e_1_3_3_24_2","doi-asserted-by":"publisher","DOI":"10.5339\/gcsp.2013.10"},{"key":"e_1_3_3_25_2","doi-asserted-by":"publisher","DOI":"10.1016\/s0002-9149(83)80105-2"},{"key":"e_1_3_3_26_2","doi-asserted-by":"publisher","DOI":"10.1038\/ng.3656"},{"key":"e_1_3_3_27_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41588-021-01006-7"},{"key":"e_1_3_3_28_2","doi-asserted-by":"publisher","DOI":"10.1038\/nbt.4235"},{"key":"e_1_3_3_29_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41588-021-00783-5"}],"container-title":["Circulation: Genomic and Precision Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.ahajournals.org\/doi\/full\/10.1161\/CIRCGEN.123.004470","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,5,29]],"date-time":"2025-05-29T21:13:13Z","timestamp":1748553193000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.ahajournals.org\/doi\/10.1161\/CIRCGEN.123.004470"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,10]]},"references-count":28,"journal-issue":{"issue":"5","published-print":{"date-parts":[[2024,10]]}},"alternative-id":["10.1161\/CIRCGEN.123.004470"],"URL":"https:\/\/doi.org\/10.1161\/circgen.123.004470","relation":{},"ISSN":["2574-8300"],"issn-type":[{"value":"2574-8300","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,10]]},"assertion":[{"value":"2023-10-26","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-06-16","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-08-08","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}