Scheike Thomas H, Holst Klaus K, Hjelmborg Jacob B
Department of Biostatistics, University of Copenhagen, Øster Farimagsgade 5, 1014, Copenhagen, Denmark,
Lifetime Data Anal. 2015 Apr;21(2):280-99. doi: 10.1007/s10985-014-9309-5. Epub 2014 Sep 4.
We consider data from the Danish twin registry and aim to study in detail how lifetimes for twin-pairs are correlated. We consider models where we specify the marginals using a regression structure, here Cox's regression model or the additive hazards model. The best known such model is the Clayton-Oakes model. This model can be extended in several directions. One extension is to allow the dependence parameter to depend on covariates. Another extension is to model dependence via piecewise constant cross-hazard ratio models. We show how both these models can be implemented for large sample data, and suggest a computational solution for obtaining standard errors for such models for large registry data. In addition we consider alternative models that have some computational advantages and with different dependence parameters based on odds ratios of the survival function using the Plackett distribution. We also suggest a way of assessing how and if the dependence is changing over time, by considering either truncated or right-censored versions of the data to measure late or early dependence. This can be used for formally testing if the dependence is constant, or decreasing/increasing. The proposed procedures are applied to Danish twin data to describe dependence in the lifetimes of the twins. Here we show that the early deaths are more correlated than the later deaths, and by comparing MZ and DZ associations we suggest that early deaths might be more driven by genetic factors. This conclusion requires models that are able to look at more local dependence measures. We further show that the dependence differs for MZ and DZ twins and appears to be the same for males and females, and that there are indications that the dependence increases over calendar time.
我们研究了来自丹麦双胞胎登记处的数据,旨在详细探讨双胞胎对的寿命是如何相互关联的。我们考虑了一些模型,在这些模型中,我们使用回归结构来指定边缘分布,这里采用Cox回归模型或相加风险模型。最著名的此类模型是Clayton-Oakes模型。该模型可以在几个方向上进行扩展。一种扩展是允许依赖参数依赖于协变量。另一种扩展是通过分段常数交叉风险比模型对依赖关系进行建模。我们展示了如何针对大样本数据实现这两种模型,并针对大型登记数据为此类模型获取标准误差提出了一种计算解决方案。此外,我们还考虑了具有一些计算优势且基于使用Plackett分布的生存函数的优势比具有不同依赖参数的替代模型。我们还提出了一种评估依赖关系如何以及是否随时间变化的方法,即通过考虑数据的截断或右删失版本来衡量晚期或早期依赖。这可用于正式检验依赖关系是否恒定,或是否在减少/增加。所提出的程序应用于丹麦双胞胎数据,以描述双胞胎寿命中的依赖关系。在这里,我们表明早期死亡比晚期死亡的相关性更强,并且通过比较同卵双胞胎(MZ)和异卵双胞胎(DZ)的关联,我们认为早期死亡可能更多地由遗传因素驱动。这一结论需要能够查看更多局部依赖度量的模型。我们进一步表明,MZ和DZ双胞胎的依赖关系不同,并且对于男性和女性似乎是相同的,而且有迹象表明依赖关系随日历时间增加。