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A Precision Environment-Wide Association Study of Hypertension via Supervised Cadre Models
IEEE Journal of Biomedical and Health Informatics ( IF 7.7 ) Pub Date : 2020-03-01 , DOI: 10.1109/jbhi.2019.2918070
Alexander New , Kristin P Bennett

We consider the problem in precision health of grouping people into subpopulations based on their degree of vulnerability to a risk factor. These subpopulations cannot be discovered with traditional clustering techniques because their quality is evaluated with a supervised metric: The ease of modeling a response variable for observations within them. Instead, we apply the more appropriate supervised cadre model (SCM). We extend the SCM formalism so that it may be applied to multivariate regression and binary classification problems and develop a way to use conditional entropy to assess the confidence in the process by which a subject is assigned their cadre. Using the SCM, we generalize the environment-wide association study (EWAS) to be able to model heterogeneity in population risk. In our EWAS, we consider more than 200 environmental exposure factors and find their association with diastolic blood pressure, systolic blood pressure, and hypertension. This requires adapting the SCM to be applicable to data generated by a complex survey design. After correcting for false positives, we found 25 exposure variables that had a significant association with at least one of our response variables. Eight of these were significant for a discovered subpopulation but not for the overall population. Some of these associations have been identified by previous researchers, whereas others appear to be novel. We examine discovered subpopulations in detail, finding that they are interpretable and suggestive of further research questions.

中文翻译:

通过监督干部模型对高血压进行精确的全环境关联研究

我们根据人们对风险因素的脆弱程度,将人们分组为亚人群来考虑精准健康方面的问题。这些亚群无法通过传统的聚类技术发现,因为它们的质量是通过监督指标来评估的:为响应变量建模以简化其内部观测的简便性。相反,我们应用更合适的监督干部模型(SCM)。我们扩展了SCM形式主义,以便可以将其应用于多元回归和二元分类问题,并开发一种使用条件熵来评估对象分配干部过程的置信度的方法。使用SCM,我们可以对整个环境的关联研究(EWAS)进行概括,以便能够对人口风险中的异质性进行建模。在我们的EWAS中 我们考虑了200多种环境暴露因素,并发现它们与舒张压,收缩压和高血压有关。这就要求调整SCM,使其适用于复杂的调查设计生成的数据。纠正误报后,我们发现了25个暴露变量,这些变量与至少一个响应变量有显着关联。其中有8个对发现的亚种群具有重要意义,但对总人口却没有意义。这些关联中的某些已经由先前的研究人员确定,而其他关联似乎是新颖的。我们详细检查了发现的亚群,发现它们是可解释的并暗示了进一步的研究问题。这就要求调整SCM,使其适用于复杂的调查设计生成的数据。纠正误报后,我们发现了25个暴露变量,这些变量与至少一个响应变量有显着关联。其中有8个对发现的亚种群具有重要意义,但对总人口却没有意义。这些关联中的某些已经由先前的研究人员确定,而其他关联似乎是新颖的。我们详细检查了发现的亚群,发现它们是可解释的并暗示了进一步的研究问题。这就要求调整SCM,使其适用于复杂的调查设计生成的数据。纠正误报后,我们发现了25个暴露变量,这些变量与至少一个响应变量有显着关联。其中有8个对发现的亚种群具有重要意义,但对总人口却没有意义。这些关联中的某些已经由先前的研究人员确定,而其他关联似乎是新颖的。我们详细检查了发现的亚群,发现它们是可解释的并暗示了进一步的研究问题。其中有8个对发现的亚种群具有重要意义,但对总人口却没有意义。这些关联中的某些已经由先前的研究人员确定,而其他关联似乎是新颖的。我们详细检查了发现的亚群,发现它们是可解释的并暗示了进一步的研究问题。其中有8个对发现的亚种群具有重要意义,但对总人口却没有意义。这些关联中的某些已经由先前的研究人员确定,而其他关联似乎是新颖的。我们详细检查了发现的亚群,发现它们是可解释的并暗示了进一步的研究问题。
更新日期:2020-03-01
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