Yu Zhaoxia
Department of Statistics, University of California, Irvine, CA 92697, USA.
Hum Hered. 2011;71(3):171-9. doi: 10.1159/000327355. Epub 2011 Jul 20.
The case-parents design has been widely used to detect genetic associations as it can prevent spurious association that could occur in population-based designs. When examining the effect of an individual genetic locus on a disease, logistic regressions developed by conditioning on parental genotypes provide complete protection from spurious association caused by population stratification. However, when testing gene-gene interactions, it is unknown whether conditional logistic regressions are still robust. Here we evaluate the robustness and efficiency of several gene-gene interaction tests that are derived from conditional logistic regressions. We found that in the presence of SNP genotype correlation due to population stratification or linkage disequilibrium, tests with incorrectly specified main-genetic-effect models can lead to inflated type I error rates. We also found that a test with fully flexible main genetic effects always maintains correct test size and its robustness can be achieved with negligible sacrifice of its power. When testing gene-gene interactions is the focus, the test allowing fully flexible main effects is recommended to be used.
病例-父母设计已被广泛用于检测基因关联，因为它可以防止在基于人群的设计中可能出现的虚假关联。在研究单个基因座对疾病的影响时，通过对父母基因型进行条件设定而开发的逻辑回归能够完全防止因人群分层导致的虚假关联。然而，在测试基因-基因相互作用时，条件逻辑回归是否仍然稳健尚不清楚。在此，我们评估了几种源自条件逻辑回归的基因-基因相互作用测试的稳健性和效率。我们发现，在由于人群分层或连锁不平衡导致单核苷酸多态性（SNP）基因型相关的情况下，主基因效应模型指定错误的测试可能会导致第一类错误率膨胀。我们还发现，具有完全灵活主基因效应的测试始终能保持正确的检验规模，并且在其功效牺牲可忽略不计的情况下就能实现其稳健性。当以测试基因-基因相互作用为重点时，建议使用允许主效应完全灵活的测试。
