Medland Sarah E, Neale Michael C, Eaves Lindon J, Neale Benjamin M
Genetic Epidemiology Unit, Queensland Institute of Medical Research, Brisbane, Queensland, Australia.
Behav Genet. 2009 Mar;39(2):220-9. doi: 10.1007/s10519-008-9247-7. Epub 2008 Dec 14.
Following the publication of Purcell's approach to the modeling of gene by environment interaction in 2002, the interest in G x E modeling in twin and family data increased dramatically. The analytic techniques described by Purcell were designed for use with continuous data. Here we explore the re-parameterization of these models for use with ordinal and binary outcome data. Analysis of binary and ordinal data within the context of a liability threshold model traditionally requires constraining the total variance to unity to ensure identification. Here, we demonstrate an alternative approach for use with ordinal data, in which the values of the first two thresholds are fixed, thus allowing the total variance to change as function of the moderator. We also demonstrate that when using binary data, constraining the total variance to unity for a given value of the moderator is sufficient to ensure identification. Simulation results indicate that analyses of ordinal and binary data can recover both the raw and standardized patterns of results. However, the scale of the results is dependent on the specification of (threshold or variance) constraints rather than the underlying distribution of liability. Example Mx scripts are provided.
2002年珀塞尔关于基因与环境相互作用建模方法发表之后,对双胞胎和家庭数据中基因与环境相互作用建模的兴趣急剧增加。珀塞尔所描述的分析技术是为连续数据设计的。在此,我们探索将这些模型重新参数化以用于有序和二元结局数据。在 liability threshold 模型的背景下,对二元和有序数据的分析传统上需要将总方差约束为1以确保可识别性。在此,我们展示一种用于有序数据的替代方法,其中前两个阈值的值是固定的,从而允许总方差作为调节变量的函数而变化。我们还证明,当使用二元数据时,对于给定的调节变量值将总方差约束为1足以确保可识别性。模拟结果表明,对有序和二元数据的分析可以恢复原始和标准化的结果模式。然而,结果的规模取决于(阈值或方差)约束的设定,而不是 liability 的潜在分布。提供了示例Mx脚本。