Assessing the influence of a genetic characteristic on disease in the presence of a strong environmental etiology.

An inference as to the possible causal role of a genetic characteristic in the development of a disease is strengthened when there is a large disparity in disease incidence between persons with and without that characteristic. If the disparity is particularly great when, based on the presence or absence of a strong environmental risk factor, we would predict it to be so, then a causal inference is further strengthened. Only analyses that focus on the gene-disease association, conditional on the environmental factor, directly bear on the etiologic role of the genetic characteristic.