A general guide to control selection for any case-control study is that controls should be selected from the same population in which cases arose, and should be representative of the population who would have become cases according to the case definition and recruitment strategies for the study 19. This has long been the golden rule in epidemiological study design, the reason being that it minimises spurious findings (‘false positives’) due to information and selection biases, and CONFOUNDING 20. In genetic association studies, bias due to environmental factors is not generally a problem; the most important type of bias - confounding - is related to the ethnic origin of cases and controls, and is often referred to as POPULATION STRATIFICATION 21. In this situation, a comparison of the frequency of the genetic variant between cases and controls will show a significant difference due to the underlying sampling scheme rather than to a real effect of the variant on disease risk.
