The research problem we address here is how to use both case–control and family-based data in a test for association that is powerful yet robust to population stratification. Toward this purpose, the combined association analysis method was developed by Nagelkerke et al. [25] and refined by Epstein et al. [26]. Those approaches provide greater power in association studies than using either case–control or family-based samples separately. The drawback is that they make a strong assumption about the sample with respect to population structure. If the assumption fails, the tests can lead to spurious associations. Although this assumption can be met by particularly well-planned studies, it is impossible to guarantee if data are combined across many studies.
