Frequencies of complex diseases in hybrid populations

Diseases of complex etiology demonstrate considerable variation in their frequencies in different ethnic populations. Noninsulin-dependent diabetes mellitus (NIDDM), rheumatoid arthritis, and several cardiovascular diseases constitute examples of such disorders. In genetic studies involving hybrid populations of known ancestry, it is of interest to compare and correlate disease prevalence with the admixture proportion, the latter estimated from a number of polymorphic genetic markers. Theoretical formulations are provided relating disease prevalence in a hybrid population to the admixture proportion under different models of disease transmission. It is shown that the relationship between admixture proportion and disease frequency provides discriminatory power regarding the mode of inheritance. This method is illustrated with an example comparing the proportion of Amerindian ancestry in Mexican-Americans and the prevalence of NIDDM. It is found that genetic factors are involved in susceptibility to NIDDM, but the mode of inheritance cannot be explained by any simple genetic model, and the role of sporadic events cannot be totally ruled out.