Maternal Gene-Environment Effects: An Evaluation of Statistical Approaches to Detect Effects and an Investigation of the Effect of Violations of Model Assumptions

Abstract

Discovering the associations between genetic variables and disease status can help reduce the burden of disease on society. This thesis focuses on the methods required to detect maternal genetic effects (an effect where the genes of the mother affect the disease risk of the child) and interaction effects between these maternal genes and environmental variables in trio data consisting of parents and an affected child. A simulation study was conducted to determine the extent to which testing for these effects is affected by violations to the mating symmetry assumption required for two current methods when control parents are not available.. This study showed that methods for maternal effect estimation are not robust to these violations; however, the interaction test is robust to the violation. Finally, a candidate gene study on orofacial clefts was conducted to evaluate maternal gene-environment interactions in international consortium data. Significant effects were found but the large magnitude of the effect estimates raises concerns about the validity of the results. This thesis tries also discusses the lack of methods and software available to estimate maternal gene environment interactions.