Abstract：
UNASSIGNED: Coronary atherosclerotic burden and adverse coronary heart disease events are related phenotypes with likely shared genetic cause.
UNASSIGNED: 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.
UNASSIGNED: 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.
UNASSIGNED: 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.
UNASSIGNED: 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.
UNASSIGNED: 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.
UNASSIGNED: 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.
摘要：
■冠状动脉粥样硬化负担和不良冠心病事件是相关的表型，可能具有共同的遗传原因。
■我们分析了6021例冠状动脉造影患者，基因分型，和外显子组测序数据。我们测试了冠心病（PRSCHD）的多基因风险评分与多种冠状动脉疾病（CAD）严重程度的相关性。我们评估了3种家族性高胆固醇血症基因中PRSCHD与致病/可能致病变异之间的相互作用。我们进行了中介分析，以探讨CAD严重程度是否介导了PRSCHD与流行冠心病和急性心肌梗死的相关性。
■PRSCHD的1-SD增加与CAD严重程度的多种指标相关，包括对数Gensini评分(β，0.31[95%CI，0.28-0.33]）。在校正PRSCHD后，携带致病性/可能致病性家族性高胆固醇血症变异与更高的logGensini评分相关（β，0.21[95%CI，0.03-0.38]）。PRSCHD与平均9.2年随访期间的心肌梗死相关（风险比，1.20[95%CI，1.13-1.27]；P=5×10-10)，Gensini评分介导了90%的关联。
■PRSCHD与多种CAD严重程度指标相关。PRSCHD与心肌梗死的相关性几乎完全由CAD严重程度介导，表明两种表型之间存在相当大的遗传重叠。
■我们分析了6021例冠状动脉造影患者，基因分型，和外显子组测序数据。我们测试了冠心病（PRSCHD）的多基因风险评分与多种冠状动脉疾病（CAD）严重程度的相关性。我们评估了3种家族性高胆固醇血症基因中PRSCHD与致病/可能致病变异之间的相互作用。我们进行了中介分析，以探讨CAD严重程度是否介导了PRSCHD与流行冠心病和急性心肌梗死的相关性。
■PRSCHD的1-SD增加与CAD严重程度的多种指标相关，包括对数Gensini评分(β，0.31[95%CI，0.28-0.33]）。在校正PRSCHD后，携带致病性/可能致病性家族性高胆固醇血症变异与更高的logGensini评分相关（β，0.21[95%CI，0.03-0.38]）。PRSCHD与平均9.2年随访期间的心肌梗死相关（风险比，1.20[95%CI，1.13-1.27]；P=5×10-10)，Gensini评分介导了90%的关联。
■PRSCHD与多种CAD严重程度指标相关。PRSCHD与心肌梗死的相关性几乎完全由CAD严重程度介导，表明两种表型之间存在相当大的遗传重叠。
