Many chronic diseases are caused by the interaction of genes and environmental factors. Genetic epidemiologic research seeks to elucidate the role of genetic factors and their interaction with environmental factors in the occurrence of disease. Gene-environment interaction can be assessed using different types of case-control comparisons. The classic case-control design is suitable to investigate the association between multiple genes and environmental factors. Results can be presented in a two-by-four table. In a case-parents design, the genotype of each case is compared with the genotype of a fictitious control formed by the non-transmitted alleles from each parent. In a case-only design, the relationship between a genotype and an environmental factor is examined in a population of affected cases only. Both the case-parents and the case-only designs assume independence between genotype and environmental factors in the control group.