Mitchell Laura E, Weinberg Clarice R
Center for Environmental and Genetic Medicine, Institute of Biosciences and Technology, Texas AandM University System Health Sciences Center, Houston, TX 77030, USA.
Am J Epidemiol. 2005 Oct 1;162(7):676-85. doi: 10.1093/aje/kwi249. Epub 2005 Aug 10.
Diseases that develop during gestation may be influenced by the genotype of the mother and the inherited genotype of the embryo/fetus. However, given the correlation between maternal and offspring genotypes, differentiating between inherited and maternal genetic effects is not straightforward. The two-step transmission disequilibrium test was the first, family-based test proposed for the purpose of differentiating between maternal and offspring genetic effects. However, this approach, which requires data from "pents" comprising an affected child, mother, father, and maternal grandparents, provides biased tests for maternal genetic effects when the offspring genotype is associated with disease. An alternative approach based on transmissions from grandparents provides unbiased tests for maternal and offspring genetic effects but requires genotype information for paternal grandparents in addition to pents. The authors have developed two additional, pent-based approaches for the evaluation of maternal and offspring genetic effects. One approach requires the assumption of genetic mating type symmetry (pent-1), whereas the other does not (pent-2). Simulation studies demonstrate that both of these approaches provide valid estimation and testing for offspring and maternal genotypic effects. In addition, the power of the pent-1 approach is comparable with that of the approach based on data using all four grandparents.
孕期发生的疾病可能受母亲的基因型以及胚胎/胎儿的遗传基因型影响。然而，鉴于母体与后代基因型之间的相关性，区分遗传效应和母体遗传效应并非易事。两步传递不平衡检验是首个为区分母体和后代遗传效应而提出的基于家系的检验方法。然而，这种方法需要来自由患病儿童、母亲、父亲和外祖父母组成的“五口之家”的数据，当后代基因型与疾病相关时，会对母体遗传效应进行有偏检验。一种基于祖父母传递的替代方法能对母体和后代遗传效应进行无偏检验，但除了“五口之家”外还需要祖父祖母的基因型信息。作者还开发了另外两种基于“五口之家”的方法来评估母体和后代的遗传效应。一种方法需要假设遗传交配类型对称（五口之家 - 1），而另一种则不需要（五口之家 - 2）。模拟研究表明，这两种方法都能对后代和母体基因型效应进行有效估计和检验。此外，五口之家 - 1方法的检验效能与基于使用所有四位祖父母数据的方法相当。
