Department of Biostatistics and Informatics, Colorado School of Public Health, University of Colorado Anschutz Medical Campus, Aurora, U.S.A.
Stat Med. 2014 Jan 30;33(2):304-18. doi: 10.1002/sim.5930. Epub 2013 Aug 6.
The study of gene-environment interactions is an increasingly important aspect of genetic epidemiological investigation. Historically, it has been difficult to study gene-environment interactions using a family-based design for quantitative traits or when parent-offspring trios were incomplete. The QBAT-I provides researchers a tool to estimate and test for a gene-environment interaction in families of arbitrary structure that are sampled without regard to the phenotype of interest, but is vulnerable to inflated type I error if families are ascertained on the basis of the phenotype. In this study, we verified the potential for type I error of the QBAT-I when applied to samples ascertained on a trait of interest. The magnitude of the inflation increases as the main genetic effect increases and as the ascertainment becomes more extreme. We propose an ascertainment-corrected score test that allows the use of the QBAT-I to test for gene-environment interactions in ascertained samples. Our results indicate that the score test and an ad hoc method we propose can often restore the nominal type I error rate, and in cases where complete restoration is not possible, dramatically reduce the inflation of the type I error rate in ascertained samples.
基因-环境相互作用的研究是遗传流行病学调查中一个日益重要的方面。从历史上看，使用基于家庭的设计来研究定量特征或当父母-子女三体型不完全时，研究基因-环境相互作用一直很困难。QBAT-I 为研究人员提供了一种工具，可以在不考虑感兴趣的表型的情况下，对任意结构的家庭进行基因-环境相互作用的估计和检验，但如果家庭是根据表型确定的，则容易导致 I 型错误膨胀。在这项研究中，我们验证了当 QBAT-I 应用于基于感兴趣特征的样本时，I 型错误的可能性。随着主要遗传效应的增加和确定变得更加极端，通货膨胀的幅度也会增加。我们提出了一种确定校正评分检验，允许使用 QBAT-I 在确定的样本中检验基因-环境相互作用。我们的结果表明，评分检验和我们提出的一种特定方法通常可以恢复名义 I 型错误率，并且在无法完全恢复的情况下，显著降低确定样本中 I 型错误率的膨胀。
