Genetic Risk Score for Coronary Disease Identifies Predispositions to Cardiovascular and Noncardiovascular Diseases
Genetic Risk Score for Coronary Disease Identifies Predispositions to Cardiovascular and Noncardiovascular Diseases
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DOI：
10.1016/j.jacc.2019.03.512
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发表时间：
2019-06-18
影响因子：
24
通讯作者：
Schunkert, Heribert
中科院分区：
文献类型：
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作者：
Ntalla, Ioanna;Kanoni, Stavroula;Schunkert, Heribert
背景心血管（CV）疾病的分类分为广泛的临床实体。许多这样的疾病在特定的患者群体中一致，并建议共享predisposities. Acceptives这项研究的重点是冠状动脉疾病（CAD），并调查了遗传关系，CV和非CV疾病与报告的CAD comorembryos.METHODS这项研究检查了425,196英国生物库参与者，以确定遗传风险评分（GRS）的基础上300 CAD相关的变异（CAD-GRS）。该评分与22个特征相关，包括风险因素、继发于CAD的疾病以及共病和非CV疾病。结果高胆固醇血症（OR：1.27; 95% CI：1.26 ~ 1.29）和高血压（OR：1.11; 95% CI：1.10 ~ 1.12）与CAD-GRS密切相关，提示CAD-GRS评分包含易患这些疾病的变异。然而，在无CAD危险因素的CAD患者中，CAD-GRS也具有显著性（OR：1.37; 95%CI：1.30 - 1.44）。该研究观察到CAD-GRS与外周动脉疾病之间存在显著相关性（OR：1.28; 95% CI：1.23 - 1.32），腹主动脉瘤（OR：1.28; 95% CI：1.20 - 1.37），和卒中（OR：1.08; 95%CI：1.05至1.10），在敏感性分析中仍显着，表明共享的遗传易感性。该评分还与心力衰竭（OR：1.25; 95% CI：1.22 - 1.29）、房颤（OR：1.08; 95% CI：1.05 - 1.10）和过早死亡（OR：1.04; 95% CI：1.02 - 1.06）相关。这些关联在敏感性分析中被消除，表明它们继发于流行的CAD。最后，分数和偏头痛（OR：0.94; 95%CI：0.93至0.96）之间观察到负相关。结论广泛的CV条件，包括过早死亡，可能连续或平行开发CAD相同的遗传根源。在心力衰竭等疾病中，该研究发现CAD-GRS可用于对与CAD风险没有或有限遗传重叠的患者进行分层。CAD的遗传易感性增加与偏头痛呈负相关。(C)2019年由美国心脏病学会基金会。
BACKGROUND The taxonomy of cardiovascular (CV) diseases is divided into a broad spectrum of clinical entities. Many such diseases coincide in specific patient groups and suggest shared predisposition.OBJECTIVES This study focused on coronary artery disease (CAD) and investigated the genetic relationship to CV and non-CV diseases with reported CAD comorbidity.METHODS This study examined 425,196 UK Biobank participants to determine a genetic risk score (GRS) based on 300 CAD associated variants (CAD-GRS). This score was associated with 22 traits, including risk factors, diseases secondary to CAD, as well as comorbid and non-CV conditions. Sensitivity analyses were performed in individuals free from CAD or stable angina diagnosis.RESULTS Hypercholesterolemia (odds ratio [OR]: 1.27; 95% CI: 1.26 to 1.29) and hypertension (OR: 1.11; 95% CI: 1.10 to 1.12) were strongly associated with the CAD-GRS, which indicated that the score contained variants predisposing to these conditions. However, the CAD-GRS was also significant in patients with CAD who were free of CAD risk factors (OR: 1.37; 95% CI: 1.30 to 1.44). The study observed significant associations between the CAD-GRS and peripheral arterial disease (OR: 1.28; 95% CI: 1.23 to 1.32), abdominal aortic aneurysms (OR: 1.28; 95% CI: 1.20 to 1.37), and stroke (OR: 1.08; 95% CI: 1.05 to 1.10), which remained significant in sensitivity analyses that suggested shared genetic predisposition. The score was also associated with heart failure (OR: 1.25; 95% CI: 1.22 to 1.29), atrial fibrillation (OR: 1.08; 95% CI: 1.05 to 1.10), and premature death (OR: 1.04; 95% CI: 1.02 to 1.06). These associations were abolished in sensitivity analyses that indicated that they were secondary to prevalent CAD. Finally, an inverse association was observed between the score and migraine headaches (OR: 0.94; 95% CI: 0.93 to 0.96).CONCLUSIONS A wide spectrum of CV conditions, including premature death, might develop consecutively or in parallel with CAD for the same genetic roots. In conditions like heart failure, the study found evidence that the CAD-GRS could be used to stratify patients with no or limited genetic overlap with CAD risk. Increased genetic predisposition to CAD was inversely associated with migraine headaches. (C) 2019 by the American College of Cardiology Foundation.