There are several conditions that determine whether a population-based case-control study is suitable to answer specific research questions. First, such a study design is best suited to phenotypes for which several thousands of cases can be recruited to be able to detect the likely modest underlying genetic relative risks. The power of a case-control study can potentially be increased (and thus the number of cases required decreased) by recruiting cases with a family history of the condition (or even by selecting multiple cases from families whilst adjusting for their familial correlation) as they may be more homogeneous in genetic aetiology. This is also known as enrichment sampling 18. However, enrichment sampling does not always increase power in genetic studies (as familial aggregation may also be due to shared environmental factors, or due to genetic variants not under consideration), while general population-based samples can provide more power. If the case definition is a relatively rare sub-phenotype that shows clear segregation in families (and families with multiple affecteds can be collected and genotyped), then a family-based approach will be preferable. A second
