动脉粥样硬化性心血管疾病(ASCVD)是全球主要的死亡原因,个体筛查应该基于行为,新陈代谢,和从大型人群研究中收集的数据得出的遗传概况。由于ASCVD的多基因性质,我们旨在评估基因组学与ASCVD风险的关联及其对急性心肌梗死发生的影响,中风,或人群水平的外周动脉血栓性缺血事件。心血管基因(CV-GENES)是一个全国性的,多中心,1:1巴西3,734例患者的病例对照研究。病例的纳入标准是首次出现ASCVD事件之一。没有已知ASCVD的个人将有资格作为对照。核心实验室将通过低通全基因组测序和全外显子组测序进行遗传分析。为了估计遗传多态性与ASCVD之间的独立关联,多基因风险评分(PRS)将通过混合方法建立,包括每个单核苷酸多态性(SNP)的效应大小,观察到的效应等位基因数量,样本倍性,PRS中包含的SNP总数,和样品中未缺失的SNP的数量。此外,致病性或可能致病性变异的存在将在8个基因(ABCG5,ABCG8,APOB,APOE,LDLR,LDLRAP1,LIPA,PCSK9)与动脉粥样硬化有关。多元逻辑回归将用于估计调整后的优势比(OR)和95%置信区间(CI),并计算人口可归因风险。临床试验注册:本研究已在clinicaltrials.gov(NCT05515653)中注册。
Atherosclerotic Cardiovascular Disease (ASCVD) represents the leading cause of death worldwide, and individual screening should be based on behavioral, metabolic, and genetic profile derived from data collected in large population-based studies. Due to the polygenic nature of ASCVD, we aimed to assess the association of genomics with ASCVD risk and its impact on the occurrence of acute myocardial infarction, stroke, or peripheral artery thrombotic-ischemic events at population level. CardioVascular Genes (CV-GENES) is a nationwide, multicenter, 1:1
case-control study of 3,734 patients in Brazil. Inclusion criterion for cases is the first occurrence of one of the ASCVD events. Individuals without known ASCVD will be eligible as controls. A core lab will perform the genetic analyses through low-pass whole genome sequencing and whole exome sequencing. In order to estimate the independent association between genetic polymorphisms and ASCVD, a polygenic risk score (PRS) will be built through a hybrid approach including effect size of each Single Nucleotide Polymorphism (SNP), number of effect alleles observed, sample ploidy, total number of SNPs included in the PRS, and number of non-missing SNPs in the sample. In addition, the presence of pathogenic or likely pathogenic variants will be screened in 8 genes (ABCG5, ABCG8, APOB, APOE, LDLR, LDLRAP1, LIPA, PCSK9) associated with atherosclerosis. Multiple logistic regression will be applied to estimate adjusted odds ratios (OR) and 95% confidence intervals (CI), and population attributable risks will be calculated. Clinical trial registration: This study is registered in clinicaltrials.gov (NCT05515653).