Beyond Disease Susceptibility: Genetics, Prediction, and the Limits of Inferring Human Potential

This narrative review examines the expansion of human genetics beyond disease susceptibility to variation in human function, development, and phenotypic outcomes. In this regard, we define human potential as genetically influenced variation in what individuals may develop or achieve under different biological and environmental conditions. Its genetic architecture is highly polygenic and shaped by pleiotropy, genetic background, developmental and regulatory context, gene–environment interplay, and genetic influences on response and adaptation. Similar observed phenotypes can arise through different genetic routes, while individuals with similar baseline function may differ in their responses to environmental conditions or interventions. Genetic prediction of these traits remains incomplete and strongly dependent on population and context. Polygenic scores developed in European-ancestry populations may show systematically different score distributions in populations underrepresented in genomic discovery datasets. Between-population differences in polygenic-score means cannot be interpreted as differences in intrinsic human capacity. Such differences can produce scientifically invalid comparisons and discriminatory use of genetic prediction. Genetic information concerning human potential should be used conscientiously, particularly in education, employment, insurance, reproduction, or decisions affecting children before the relevant phenotype has developed.