Differences in population genetic structure and substructure between cases and controls can lead to false positive association tests [1–5]. Interest in this issue has accelerated with the application of whole genome association (WGA) screens for deciphering the genetics of complex diseases. The importance of recognizing and controlling for population structure is magnified when population controls are not closely matched to cases, a process that requires multiple demographic considerations and similar sample acquisition methods. These conditions are difficult and often not practical to fulfill completely. Since many studies focus on participants of European descent, the potential impact of European substructure on association testing has specifically engendered interest [6,7]. In fact, the current study was undertaken as part of an effort to effectively ascertain and adjust for differences in population substructure among cases and controls in our studies of the genetics of rheumatoid arthritis in a participant set that predominantly includes participants of European descent.
