Inbreeding and Diseases: Demographic, Genetic, and Epidemiologic Perspectives

Abstract

The demographic and quantitative genetic aspects of consanguineous marriages are reviewed before epidemiologic principles are applied to the hundreds of studies reviewed, and 3 in particular. Consanguineous unions range from cousin-cousin to more distant relatedness, and their prevalence varies by culture. Prevalence is highest in Arab countries, followed by India, Japan, Brazil and Israel. They are most common in lower educational and socioeconomic groups, the traditionally religious, and the early married, but are declining with modernization. Consanguinity is measured by geneticists by the inbreeding coefficient, the mean consanguinity of a population, and the concept of genetic load. Recessive genes may be deleterious or beneficial if heterozygous in local conditions. Bayesian statistics can predict by the coefficient of increase the probability of disease in offspring as a function of consanguinity and disease characteristics. Inbreeding generally increases prereproductive mortality; crude mortality increases with inbreeding in proportion to the mortality rate. Morbidity increases significantly with inbreeding in many diseases studies in many countries. Epidemiologic studies usually measure inbreeding effects in terms of genetic load, which is not readily translatable into morbidity and mortality. Several methods of computing results of epidemiologic studies are discussed, as well as methodological study design problems. Confounding is the most difficult problem in these studies, because of the difficulty in selecting non-inbred controls. Future inbreeding studies should be interpreted based on both genetic and epidemiologic grounds to illuminate the role of genetic factors and the relevance of inbreeding to disease and public health.