phenotypes and/or strong family history) will have limited the proportions of controls meeting case criteria to low levels (for example, to <5%). Although a study design which used ‘hypercontrols’ (that is, selection of control individuals from the lower extremity of the relevant trait distribution) would generally be the most powerful approach in a study focusing on one disease, the merits of such an approach need to be weighed against the additional costs associated with the need to phenotype and genotype each control sample.
