Alborz Sherafati, Kristjan Norland, Mohammadreza Naderian, Daniel J Schaid, Iftikhar J Kullo
{"title":"多基因风险与冠心病严重程度","authors":"Alborz Sherafati, Kristjan Norland, Mohammadreza Naderian, Daniel J Schaid, Iftikhar J Kullo","doi":"10.1161/CIRCGEN.123.004470","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>Coronary atherosclerotic burden and adverse coronary heart disease events are related phenotypes with likely shared genetic cause.</p><p><strong>Methods: </strong>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<sub>CHD</sub>) with multiple measures of coronary artery disease (CAD) severity. We assessed the interplay between PRS<sub>CHD</sub> and pathogenic/likely pathogenic variants in 3 familial hypercholesterolemia genes. We performed mediation analyses to explore whether CAD severity mediated the association of PRS<sub>CHD</sub> with prevalent coronary heart disease and incident myocardial infarction.</p><p><strong>Results: </strong>A 1-SD increase in PRS<sub>CHD</sub> was associated with multiple measures of CAD severity, including the log Gensini score (β, 0.31 [95% CI, 0.28-0.33]). Carrying a pathogenic/likely pathogenic familial hypercholesterolemia variant was associated with a higher log Gensini score after adjustment for PRS<sub>CHD</sub> (β, 0.21 [95% CI, 0.03-0.38]). PRS<sub>CHD</sub> was associated with incident myocardial infarction over a mean follow-up of 9.2 years (hazard ratio, 1.20 [95% CI, 1.13-1.27]; <i>P</i>=5×10<sup>-</sup><sup>10</sup>), and the Gensini score mediated 90% of this association.</p><p><strong>Conclusions: </strong>PRS<sub>CHD</sub> was associated with multiple measures of CAD severity. The association of PRS<sub>CHD</sub> with incident myocardial infarction was almost fully mediated by CAD severity, indicating a considerable genetic overlap between the 2 phenotypes.</p>","PeriodicalId":10326,"journal":{"name":"Circulation: Genomic and Precision Medicine","volume":null,"pages":null},"PeriodicalIF":6.0000,"publicationDate":"2024-08-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Polygenic Risk and Coronary Artery Disease Severity.\",\"authors\":\"Alborz Sherafati, Kristjan Norland, Mohammadreza Naderian, Daniel J Schaid, Iftikhar J Kullo\",\"doi\":\"10.1161/CIRCGEN.123.004470\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Background: </strong>Coronary atherosclerotic burden and adverse coronary heart disease events are related phenotypes with likely shared genetic cause.</p><p><strong>Methods: </strong>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<sub>CHD</sub>) with multiple measures of coronary artery disease (CAD) severity. We assessed the interplay between PRS<sub>CHD</sub> and pathogenic/likely pathogenic variants in 3 familial hypercholesterolemia genes. We performed mediation analyses to explore whether CAD severity mediated the association of PRS<sub>CHD</sub> with prevalent coronary heart disease and incident myocardial infarction.</p><p><strong>Results: </strong>A 1-SD increase in PRS<sub>CHD</sub> was associated with multiple measures of CAD severity, including the log Gensini score (β, 0.31 [95% CI, 0.28-0.33]). Carrying a pathogenic/likely pathogenic familial hypercholesterolemia variant was associated with a higher log Gensini score after adjustment for PRS<sub>CHD</sub> (β, 0.21 [95% CI, 0.03-0.38]). PRS<sub>CHD</sub> was associated with incident myocardial infarction over a mean follow-up of 9.2 years (hazard ratio, 1.20 [95% CI, 1.13-1.27]; <i>P</i>=5×10<sup>-</sup><sup>10</sup>), and the Gensini score mediated 90% of this association.</p><p><strong>Conclusions: </strong>PRS<sub>CHD</sub> was associated with multiple measures of CAD severity. The association of PRS<sub>CHD</sub> with incident myocardial infarction was almost fully mediated by CAD severity, indicating a considerable genetic overlap between the 2 phenotypes.</p>\",\"PeriodicalId\":10326,\"journal\":{\"name\":\"Circulation: Genomic and Precision Medicine\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":6.0000,\"publicationDate\":\"2024-08-08\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Circulation: Genomic and Precision Medicine\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1161/CIRCGEN.123.004470\",\"RegionNum\":2,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"CARDIAC & CARDIOVASCULAR SYSTEMS\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Circulation: Genomic and Precision Medicine","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1161/CIRCGEN.123.004470","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"CARDIAC & CARDIOVASCULAR SYSTEMS","Score":null,"Total":0}
Polygenic Risk and Coronary Artery Disease Severity.
Background: Coronary atherosclerotic burden and adverse coronary heart disease events are related phenotypes with likely shared genetic cause.
Methods: 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 (PRSCHD) with multiple measures of coronary artery disease (CAD) severity. We assessed the interplay between PRSCHD and pathogenic/likely pathogenic variants in 3 familial hypercholesterolemia genes. We performed mediation analyses to explore whether CAD severity mediated the association of PRSCHD with prevalent coronary heart disease and incident myocardial infarction.
Results: A 1-SD increase in PRSCHD was associated with multiple measures of CAD severity, including the log Gensini score (β, 0.31 [95% CI, 0.28-0.33]). Carrying a pathogenic/likely pathogenic familial hypercholesterolemia variant was associated with a higher log Gensini score after adjustment for PRSCHD (β, 0.21 [95% CI, 0.03-0.38]). PRSCHD was associated with incident myocardial infarction over a mean follow-up of 9.2 years (hazard ratio, 1.20 [95% CI, 1.13-1.27]; P=5×10-10), and the Gensini score mediated 90% of this association.
Conclusions: PRSCHD was associated with multiple measures of CAD severity. The association of PRSCHD with incident myocardial infarction was almost fully mediated by CAD severity, indicating a considerable genetic overlap between the 2 phenotypes.
期刊介绍：
Circulation: Genomic and Precision Medicine is a distinguished journal dedicated to advancing the frontiers of cardiovascular genomics and precision medicine. It publishes a diverse array of original research articles that delve into the genetic and molecular underpinnings of cardiovascular diseases. The journal's scope is broad, encompassing studies from human subjects to laboratory models, and from in vitro experiments to computational simulations.
Circulation: Genomic and Precision Medicine is committed to publishing studies that have direct relevance to human cardiovascular biology and disease, with the ultimate goal of improving patient care and outcomes. The journal serves as a platform for researchers to share their groundbreaking work, fostering collaboration and innovation in the field of cardiovascular genomics and precision medicine.
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