Simulation of Mendelism revisited: the recessive gene for attending medical school

Much of the recent confusion concerning studies of complex phenotypes such as neuropsychiatric disorders may derive from the inappropriate assumption of simple Mendelian transmission. This has sometimes led to unrealistic expectations regarding the potential benefits of linkage studies. To investigate how Mendelism may be simulated, we collected data on a common familial behavioral trait, attendance at medical school, among the relatives of 249 preclinical medical students. The "risk" of first-degree relatives going to medical school was approximately 61 times that of the general population. Complex segregation analysis carried out under a unified model provided strong evidence of vertical transmission. The results were compatible with transmission of a major effect, and a recessive model provided as satisfactory a fit as a general single-locus model. Moreover, a commonly applied test, allowing the transmission probability parameter (tau 2) to deviate from its Mendelian value, did not give a significant improvement of fit. Only a more general model where all three transmission probabilities (tau 1, tau 2, and tau 3) were unrestricted resulted in a significantly better fit than did the recessive model.