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首页> 外文会议>Pacific Symposium on Biocomputing >RISK FACTOR INTERACTIONS AND GENETIC EFFECTS ASSOCIATED WITH POST-OPERATIVE ATRIAL FIBRILLATION
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RISK FACTOR INTERACTIONS AND GENETIC EFFECTS ASSOCIATED WITH POST-OPERATIVE ATRIAL FIBRILLATION

机译：患有术后心房颤动的风险因子相互作用和遗传效应

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Postoperative Atrial Fibrillation (PoAF) is the most common arrhythmia after heart surgery, and continues to be a major cause of morbidity Due to the complexity of this condition, many genes and/or environmental factors may play a role in susceptibility. Previous findings have shown several clinical and genetic risk factors for the development of PoAF. The goal of this study was to determine whether interactions among candidate genes and a variety of clinical factors are associated with PoAF. We applied the Multifactor Dimensionality Reduction (MDR) method to detect interactions in a sample of 940 adult subjects undergoing elective procedures of the heart or great vessels, requiring general anesthesia and sternotomy or thoracotomy, where 255 developed PoAF. We took a random sample of controls matched to the 255 AF cases for a total sample size of 510 individuals. MDR is a powerful statistical approach used to detect gene-gene or gene-environment interactions in the presence or absence of statistically detectable main effects in pharmacogenomics studies. We chose polymorphisms in three (IL-6, ACE, and ApoE) candidate genes, all previously implicated in PoAF risk, and a variety of environmental factors for analysis. We detected a single locus effect of IL-6 which is able to correctly predict disease status with 58.8% (p < 0.001) accuracy. We also detected an interaction between history of AF and length of hospital stay that predicted disease status with 68.34% (p < 0.001) accuracy. These findings demonstrate the utility of novel computational approaches for the detection of disease susceptibility genes. While each of these results looks interesting, they only explain part of PoAF susceptibility. It will be important to collect a larger set of candidate genes and environmental factors to better characterize the development of PoAF. Applying this approach, we were able to elucidate potential associations with postoperative atrial fibrillation.
机译：术后心房颤动（POAF）是心脏手术后最​​常见的心律失常，并且由于这种情况的复杂性而继续成为发病率的主要原因，许多基因和/或环境因素可能在易感性中发挥作用。以前的研究结果显示了POAF的发展的几个临床和遗传危险因素。本研究的目的是确定候选基因和各种临床因素之间的相互作用是否与POAF相关。我们施加了多因素的维度减少（MDR）方法，检测在内心或大血管的选修程序的940个成年受试者的样本中检测相互作用，需要一般麻醉和胸骨切开术或胸廓切开术，其中255个发达的痘痘。我们采用随机的控制样本与255个AF案件匹配的总样本大小为510个个体。 MDR是一种强大的统计方法，用于检测在药物代理研究中存在或不存在统计学上可检测的主要效果的存在或不存在的基因 - 基因或基因环境相互作用。我们在三（IL-6，ACE和Apoe）候选基因中选择了多态性，以前涉及POAP风险，以及各种环境因素进行分析。我们检测到IL-6的单个轨迹效果，其能够正确地预测58.8％（P <0.001）精度的疾病状态。我们还检测到AF之间的历史与住院时间长度之间的互动，预测疾病状态为68.34％（P <0.001）精度。这些研究结果证明了新型计算方法检测疾病易感基因的效用。虽然这些结果中的每一个都很有趣，但他们只解释了POAF易感性的一部分。收集更大的候选基因和环境因素将是一个重要的，以更好地表征POAF的发展。应用这种方法，我们能够阐明潜在的心房颤动的潜在关联。

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