New Admixture Patterns Trigger Gene-Environment Mismatch Between APOL1 Risk Alleles And Chronic Kidney Disease Disparities

Abstract

The underlying evolutionary genetics of African Americans in North America increases their risk for chronic kidney disease and accounts, in part, for the significant health disparity observed. In this paper we suggest that a gene-environment mismatch is responsible for the high frequency of chronic kidney disease among many African Americans and that this mismatch is augmented by gene-gene interactions that enhance the pathology proliferates in a specific environmental setting of high infectious disease (specifically trypanosomiasis) and then loses its evolutionary advantage when the population is abruptly transferred to a new environment (North America) lacking these specific selective constraints. The inordinately high frequencies of chronic kidney diseases in this evolutionarily new environment are a direct result of a mismatch between the group's background genetics, adaptations to their environments of origin, and the recent migratory transition to the Americas with new selective constraints coupled with the interactions of the original genetic adaptations with other nearby genetic and non-genetic traits.