Department of Psychology, University of Oslo, Oslo, Norway.
Norwegian Institute of Public Health, Oslo, Norway.
Eur J Epidemiol. 2024 Jun;39(6):587-603. doi: 10.1007/s10654-024-01132-6. Epub 2024 Jun 16.
Epidemiological researchers often examine associations between risk factors and health outcomes in non-experimental designs. Observed associations may be causal or confounded by unmeasured factors. Sibling and co-twin control studies account for familial confounding by comparing exposure levels among siblings (or twins). If the exposure-outcome association is causal, the siblings should also differ regarding the outcome. However, such studies may sometimes introduce more bias than they alleviate. Measurement error in the exposure may bias results and lead to erroneous conclusions that truly causal exposure-outcome associations are confounded by familial factors. The current study used Monte Carlo simulations to examine bias due to measurement error in sibling control models when the observed exposure-outcome association is truly causal. The results showed that decreasing exposure reliability and increasing sibling-correlations in the exposure led to deflated exposure-outcome associations and inflated associations between the family mean of the exposure and the outcome. The risk of falsely concluding that causal associations were confounded was high in many situations. For example, when exposure reliability was 0.7 and the observed sibling-correlation was r = 0.4, about 30-90% of the samples (n = 2,000) provided results supporting a false conclusion of confounding, depending on how p-values were interpreted as evidence for a family effect on the outcome. The current results have practical importance for epidemiological researchers conducting or reviewing sibling and co-twin control studies and may improve our understanding of observed associations between risk factors and health outcomes. We have developed an app (SibSim) providing simulations of many situations not presented in this paper.
流行病学研究人员经常在非实验设计中研究危险因素与健康结果之间的关联。观察到的关联可能是因果关系,也可能受到未测量因素的干扰。同胞和同卵双生子对照研究通过比较同胞(或双胞胎)之间的暴露水平来解释家族性混杂。如果暴露与结果的关联是因果关系,那么兄弟姐妹在结果方面也应该有所不同。然而,这些研究有时可能会引入更多的偏差而不是缓解问题。暴露测量误差可能会导致结果产生偏差,并得出错误的结论,即真正的因果暴露-结果关联受到家族因素的干扰。本研究使用蒙特卡罗模拟来检验当观察到的暴露-结果关联是真正的因果关系时,同胞对照模型中测量误差引起的偏差。结果表明,降低暴露可靠性和增加暴露中的兄弟姐妹相关性会导致暴露-结果关联的膨胀和家庭平均暴露与结果之间关联的膨胀。在许多情况下,错误地得出因果关联受到干扰的结论的风险很高。例如,当暴露可靠性为 0.7,观察到的兄弟姐妹相关性为 r=0.4 时,大约 30-90%的样本(n=2000)提供了支持因果关联受到干扰的错误结论的结果,具体取决于如何解释 p 值作为对结果的家庭效应的证据。本研究结果对进行或审查同胞和同卵双生子对照研究的流行病学研究人员具有实际意义,并可能提高我们对危险因素与健康结果之间观察到的关联的理解。我们已经开发了一个应用程序(SibSim),可以模拟本文未呈现的许多情况。