Hein Rebecca, Beckmann Lars, Chang-Claude Jenny
Department of Cancer Epidemiology, German Cancer Research Center, Heidelberg, Germany.
Hum Hered. 2009;68(4):252-67. doi: 10.1159/000228923. Epub 2009 Jul 22.
We compared four haplotype-based approaches for the analysis of gene-environment interactions when haplotype-phase is ambiguous. The methods employ different versions of the expectation maximization algorithm and differ in the choice of the reference group and in the way the risk of disease is modeled (retrospective versus prospective). Furthermore, the methods are based on distinct assumptions (such as Hardy Weinberg equilibrium). The haplotype-based methods were also compared to single-marker logistic regression (LR).
We simulated case-control scenarios where the risk variant was directly genotyped (direct scenario) or in linkage disequilibrium with the genotyped markers (indirect scenario).
The retrospective methods tended to be more powerful for detecting interactions than the prospective methods. In the indirect scenarios, the power of all methods was decreased. However, the power of the retrospectives methods was high in some scenarios and the interactions may only be detectable when using these approaches. Furthermore, we observed that the precision of one prospective method was clearly lower than the precision of the retrospective methods.
For the analysis of gene-environment (GxE) interactions in case-control data, the investigated retrospective methods can be an attractive alternative to haplotype-based methods which do not account for the retrospective sampling design.
我们比较了四种基于单倍型的方法，用于在单倍型相位不明确时分析基因-环境相互作用。这些方法采用了不同版本的期望最大化算法，在参考组的选择以及疾病风险建模方式（回顾性与前瞻性）上存在差异。此外，这些方法基于不同的假设（如哈迪-温伯格平衡）。还将基于单倍型的方法与单标记逻辑回归（LR）进行了比较。
我们模拟了病例对照场景，其中风险变异体是直接基因分型的（直接场景），或者与基因分型标记处于连锁不平衡状态（间接场景）。
回顾性方法在检测相互作用方面往往比前瞻性方法更具效力。在间接场景中，所有方法的效力均有所下降。然而，回顾性方法在某些场景中的效力较高，并且可能只有使用这些方法才能检测到相互作用。此外，我们观察到一种前瞻性方法的精度明显低于回顾性方法。
对于病例对照数据中的基因-环境（GxE）相互作用分析，所研究的回顾性方法可能是不考虑回顾性抽样设计的基于单倍型方法的一个有吸引力的替代方案。
