Perry Lucas C, Chevalier Nicolas, Luciano Michelle
School of Philosophy, Psychology and Language Sciences, University of Edinburgh, Edinburgh, UK.
Genes Brain Behav. 2025 Aug;24(4):e70030. doi: 10.1111/gbb.70030.
Previous work has suggested that genetic confounding is a persistent issue in studies of environmental predictors of executive function (EF). This is largely because controlling for genetic confounding typically requires specialized samples such as twins or adoptees, which are more difficult to recruit. Polygenic scores provide a potential alternative control, scalable to smaller samples and not requiring specialized sample features. The purpose of this study was to determine if polygenic scores of EF could be used to replicate the findings of other genetic confounding studies in a less specialized sample. Confounding models showed evidence for genetic confounding in maternal education, although it was far weaker in magnitude than in other genetically informed studies. However, consistent with previous research, there were no detectable influences of indirect genetic effects on the EF polygenic score, indicating that the detected genetic confounding was likely a true genetic effect. Finally, while environmental factors other than maternal education seemed predictive of EF, confounding models showed that this was best explained by their association with maternal education. Other predictors of EF may thus be confounded environmentally, not just genetically. While polygenic scores are a promising method with a multitude of applications, in their current state they do not replicate the findings of other genetically informed studies of EF. Caution should thus be used when employing them to study genetic confounding in EF.
先前的研究表明，在执行功能（EF）环境预测因素的研究中，基因混杂是一个长期存在的问题。这主要是因为控制基因混杂通常需要特殊样本，如同卵双胞胎或领养者，而招募这些样本更加困难。多基因分数提供了一种潜在的替代控制方法，可扩展到较小样本，且不需要特殊的样本特征。本研究的目的是确定EF的多基因分数是否可用于在不太特殊的样本中复制其他基因混杂研究的结果。混杂模型显示了母亲教育程度存在基因混杂的证据，尽管其程度远低于其他基因信息研究。然而，与先前的研究一致，间接基因效应对EF多基因分数没有可检测到的影响，这表明检测到的基因混杂可能是真正的基因效应。最后，虽然除母亲教育程度外的环境因素似乎可预测EF，但混杂模型表明，这最好通过它们与母亲教育程度的关联来解释。因此，EF的其他预测因素可能不仅在基因上，而且在环境上也存在混杂。虽然多基因分数是一种有多种应用前景的方法，但就其目前的状态而言，它们无法复制其他EF基因信息研究的结果。因此，在使用它们研究EF中的基因混杂时应谨慎。
