Figure 1.

Examples of how stratification and ancestry can affect case–control association tests. In the top panel, examples of type 1 errors are shown. Population substructure can result in false-positive associations when the regional origin/ancestry of cases and controls are not matched. In the example shown, a 10% allele frequency difference in northern European compared with southern European results in a highly significant P-value (Armitage’s χ² test) when the numbers of cases and controls derived from these regions are different. The top panel also shows an example of genotyping error that can result from genotyping cases and controls using different array chips. The bottom panel illustrates how type 2 errors, false-negative results may result from heterogeneous sample sets. In this example, a true positive result may not reach an appropriate threshold for significance when the signal is diluted by a population in which the causative SNP is absent.