contributory alleles for complex diseases and in replicating positive associations suggests that many complex diseases involve numerous variants rather than a moderate number of alleles, and the influence of any given variant may depend in critical ways on the genetic and environmental background. if many alleles are required to increase susceptibility to a disease, the odds are low that the necessary combination of alleles would become concentrated in a particular group purely through drift. population substructure in genetics research one area in which population categories can be important considerations in genetics research is in controlling for confounding between population substructure, environmental exposures, and health outcomes. association studies can produce spurious results if cases and controls have differing allele frequencies for genes that are not related to the disease being studied, although the magnitude of this problem in genetic association studies is subject to debate. various methods have been developed to detect and account for population substructure, but these methods can be difficult to apply in practice. population substructure also can be used to advantage in genetic association studies. for example, populations that represent recent mixtures of geographically separated ancestral groups can exhibit longer-range linkage disequilibrium between susceptibility alleles and genetic markers than is the case for other populations. genetic studies can use this admixture linkage disequilibrium to search for disease alleles with fewer markers than would be needed otherwise. association studies also can take advantage of the contrasting experiences of racial or ethnic groups, including migrant groups, to search for interactions between particular alleles and environmental factors that might influence health.