论文标题

非均质疾病病因的无亚型平均因果关系

The Subtype-Free Average Causal Effect for Heterogeneous Disease Etiology

论文作者

Sasson, Amit, Wang, Molin, Ogino, Shuji, Nevo, Daniel

论文摘要

研究表明,暴露对疾病的影响可能会因同一疾病的不同亚型而异。但是,现有的估计和比较这些影响的方法在很大程度上忽略了因果关系。在本文中,我们研究了吸烟可能对由称为微卫星不稳定性(MSI)的性状定义的结直肠癌亚型产生的影响。我们使用主分层提出替代因果估计,即无亚型的平均因果效应(SF-ACE)。 SF-ACE是在任何暴露水平下不受其他疾病亚型的人的暴露的因果影响。我们研究了SF-ACE的非参数识别,并讨论了不同的单调性假设,这些假设比标准环境中更细微的差异。正如主要层面效应的情况一样,从数据鉴定SF-ACE的基础的假设是无法测试的,并且可能太强了。因此,我们还开发了放松这些假设的灵敏度分析方法。我们为SF-ACE提供了三个不同的估计量,包括双重稳定估计器。我们实施了来自两个大同类群体的数据的方法,以研究吸烟对大型癌症亚型的结直肠癌因果关系的异质性。

Studies have shown that the effect an exposure may have on a disease can vary for different subtypes of the same disease. However, existing approaches to estimate and compare these effects largely overlook causality. In this paper, we study the effect smoking may have on having colorectal cancer subtypes defined by a trait known as microsatellite instability (MSI). We use principal stratification to propose an alternative causal estimand, the Subtype-Free Average Causal Effect (SF-ACE). The SF-ACE is the causal effect of the exposure among those who would be free from other disease subtypes under any exposure level. We study non-parametric identification of the SF-ACE, and discuss different monotonicity assumptions, which are more nuanced than in the standard setting. As is often the case with principal stratum effects, the assumptions underlying the identification of the SF-ACE from the data are untestable and can be too strong. Therefore, we also develop sensitivity analysis methods that relax these assumptions. We present three different estimators, including a doubly-robust estimator, for the SF-ACE. We implement our methodology for data from two large cohorts to study the heterogeneity in the causal effect of smoking on colorectal cancer with respect to MSI subtypes.

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