BACKGROUND: Myocardial infarction (MI) is a complex disease caused by both lifestyle and genetic factors. This study aims to investigate the predictive value of genetic risk, in addition to traditional cardiovascular risk factors, for recurrent events following early-onset MI. METHODS: The Italian Genetic Study of Early-Onset Myocardial Infarction is a cohort study enrolling patients with MI before 45 years. Monogenic variants causing familial hypercholesterolemia were identified, and a coronary artery disease polygenic score (PGS) was calculated. Ten-fold cross-validated Cox proportional hazards models were fitted sequentially including all clinical variables, the PGS, and monogenic variants on the composite outcome of cardiovascular death, recurrent MI, stroke, or revascularization. RESULTS: During a 19.9-year follow-up, 847 (50.7%) patients experienced recurrent events. Each 1-SD higher PGS was associated with a 21% higher hazard of recurrent events (hazard ratio, 1.21 [95% CI, 1.13–1.31]; P =4.04×10 −6 ). Except for secondary prevention, PGS was the strongest determinant of recurrent event risk (C index, 0.56 [95% CI, 0.54–0.58]) compared with clinical risk factors. Overall, predictive performance of clinical risk factors (C index, 0.69 [95% CI, 0.67–0.71]) improved after adding the PGS (C index, 0.69 [95% CI, 0.68–0.71]; P =0.006). When dividing the population by PGS quintiles, the highest fifth had a 57% higher hazard of recurrent events than the lowest fifth (hazard ratio, 1.57 [95% CI, 1.26–1.96]; P =5.57×10 −5 ). CONCLUSIONS: When compared with other clinical risk factors, PGS was the strongest predictor of event recurrence among patients with an early-onset MI. Though the discriminative power of recurrent event prediction in this cohort was modest, the addition of PGS significantly improved discrimination.

Maddalena Ardissino

Elvezia Maria Paraboschi

Samuel A. Lambert

Lois G. Kim

Martin Kelemen

Giuseppe Maglietta

Antonio Crocamo

Giulia Magnani

Serena Bricoli

Luigi Vignali

Giampaolo Niccoli

Marco Tubaro

Libor Pastika

Arunashis Sau

Fu Siong Ng

Antonio de Marvao

Michael C. Honigberg

Pradeep Natarajan

Adam J. Nelson

Michael Inouye

Emanuele Di Angelantonio

Rosanna Asselta

Diego Ardissino

Adam S. Butterworth

Circulation Genomic and Precision Medicine

流通：基因组学和精准医学考虑所有类型的原始研究文章，包括在人类受试者、实验动物、体外和计算机中进行的研究。文章可能包括以下研究：临床遗传学应用于单基因或寡基因心血管疾病的诊断和管理；复杂心血管疾病的分子基础，包括全基因组关联研究、基于外显子组和基因组测序的关联研究、编码变异关联研究、遗传连锁研究、表观基因组学、转录组学、蛋白质组学、代谢组学和宏基因组学；将电子健康记录数据或患者生成的数据与上述任何方法（包括表型关联研究）或环境或生活方式因素相结合；药物基因组学；基因表达调控；基因治疗和治疗性基因组编辑；心血管疾病诊断和管理的系统生物学方法；进行上述任何研究的新方法；以及精准医学的新应用。最重要的是，我们寻求与人类心血管生物学和疾病相关的研究。

The journal "Circulation. Genomic and Precision Medicine" encompasses all types of original research articles, including studies conducted in human subjects, experimental animals, in vitro, and computational settings. Articles may cover the following research areas: clinical genetics applications in the diagnosis and management of single-gene or polygenic cardiovascular diseases; the molecular basis of complex cardiovascular diseases, including genome-wide association studies, exome and genome sequencing association studies, coding variant association studies, genetic linkage studies, epigenomics, transcriptomics, proteomics, metabolomics, and metagenomics; integration of electronic health record data or patient-generated data with any of the aforementioned methods (including phenotype association studies) or environmental and lifestyle factors; pharmacogenomics; gene expression regulation; gene therapy and therapeutic genome editing; systems biology approaches to the diagnosis and management of cardiovascular diseases; novel methods for conducting any of the above research; and new applications of precision medicine. Importantly, we seek research related to human cardiovascular biology and disease.

《Circulation. Genomic and precision medicine》期刊涵盖所有类型的原创研究文章，包括在人类受试者、实验动物、体外实验和计算机模拟中进行的研究。文章可能涉及以下研究领域：临床遗传学在单基因或多基因心血管疾病的诊断和管理中的应用；复杂心血管疾病的分子基础，包括全基因组关联研究、外显子组和基因组测序的关联研究、编码变异关联研究、遗传连锁研究、表观基因组学、转录组学、蛋白质组学、代谢组学和宏基因组学；将电子健康记录数据或患者生成的数据与上述任何方法（包括表型关联研究）或环境和生活方式因素相结合；药物基因组学；基因表达调控；基因治疗和治疗性基因组编辑；心血管疾病诊断和管理的系统生物学方法；进行上述任何研究的新方法；以及精准医学的新应用。我们特别关注与人类心血管生物学和疾病相关的研究。

Circulation. Genomic and precision medicine

Polygenic Prediction of Recurrent Events After Early-Onset Myocardial Infarction

早发性心肌梗死后复发事件的多基因预测

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医学	2
医学, 遗传学	1
医学, 心脏和心血管系统	2

Polygenic Prediction of Recurrent Events After Early-Onset Myocardial Infarction

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Category	Quartile
GENETICS & HEREDITY	1