Use of appropriate controls in rare-variant studies

Abstract

When designing a case–control study, researchers must decide whether to gather and sequence or genotype controls in parallel with cases or whether to only sequence or genotype cases and to plan on using external, perhaps publically available control data. When using rare-variant genotyping chips, gathering and using internal controls may be the obvious choice as the cost per subject is relatively low although there is still the cost of recruiting or fi nding a suitable control set. There may be more reason to use external controls for sequencing due to its relatively high cost. Ultimately, the choice often comes down to a balance between available funds, resources, and the number and uniqueness of the cases available for sequencing or genotyping. In addition, other reasons may prompt researchers to use external controls. Researchers may choose to boost their study’s sample size and potentially the power by adding in external, publically available controls to an existing internal control set.