Likelihood ratio tests for maternal and fetal genetic effects on obstetric complications

Abstract

It is well recognized that both maternal and fetal genes could contribute to susceptibility for obstetric complications. Logistic regression models are usually adopted to model the separate or joint action of maternal and fetal loci with case-control data. The standard likelihood ratio tests (LRTs) can be used to test the significance of appropriate odds ratio parameters. This method, although simple to implement, fails to exploit a unique feature of genetic epidemiology studies of obstetric complications. Specifically, it does not take into consideration the correlation between the maternal and offspring genomes. We propose novel LRT that take advantage of this information by incorporating the fact that half of a child's genome is inherited from the mother. Our methods have substantially improved power for detecting marginal, main, and interactive maternal and fetal genotype effects, as evidenced by results from extensive simulation studies. We demonstrate our new methods by applying them to the analysis of data from a pilot study of preeclampsia.