论文标题

贝叶斯综合分析和预测,用于动脉粥样硬化心血管疾病

Bayesian Integrative Analysis and Prediction with Application to Atherosclerosis Cardiovascular Disease

论文作者

Chekouo, Thierry, Safo, Sandra E.

论文摘要

心血管疾病(CVD),包括动脉粥样硬化CVD(ASCVD),是多因素疾病,在全球范围内表现出主要的经济和社会负担。为了了解ASCVD的传统风险因素,已经做出了巨大的努力,但是这些风险因素仅占ASCVD病例的一半。确定对ASCVD促成的非传统危险因素(例如遗传变异,基因)仍然是至关重要的。此外,将功能知识纳入预测模型有可能揭示与疾病风险相关的途径。我们提出了将多个OMIC数据关联,预测临床结果,允许先前的功能信息并可以适应临床协变量的贝叶斯分层因子分析模型。这些模型是由可用数据和对ASCVD的其他风险因素的需求进行的,用于对临床,人口统计学和多摩学数据的综合分析,以识别健康成年人中10年ASCVD风险的遗传变异,基因和基因途径。我们的发现揭示了与ASCVD风险高度相关的几种遗传变异,基因和基因途径。有趣的是,其中一些与CVD风险有关。可以探索其他人在CVD中的潜在角色。我们的发现强调了联合关联和预测模型中的优点。

Cardiovascular diseases (CVD), including atherosclerosis CVD (ASCVD), are multifactorial diseases that present a major economic and social burden worldwide. Tremendous efforts have been made to understand traditional risk factors for ASCVD, but these risk factors account for only about half of all cases of ASCVD. It remains a critical need to identify nontraditional risk factors (e.g., genetic variants, genes) contributing to ASCVD. Further, incorporating functional knowledge in prediction models have the potential to reveal pathways associated with disease risk. We propose Bayesian hierarchical factor analysis models that associate multiple omics data, predict a clinical outcome, allow for prior functional information, and can accommodate clinical covariates. The models, motivated by available data and the need for other risk factors of ASCVD, are used for the integrative analysis of clinical, demographic, and multi-omics data to identify genetic variants, genes, and gene pathways potentially contributing to 10-year ASCVD risk in healthy adults. Our findings revealed several genetic variants, genes and gene pathways that were highly associated with ASCVD risk. Interestingly, some of these have been implicated in CVD risk. The others could be explored for their potential roles in CVD. Our findings underscore the merit in joint association and prediction models.

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