Real world scenarios in rare variant association analysis: the impact of imbalance and sample size on the power in silico

Background The development of sequencing techniques and statistical methods provides great opportunities for identifying the impact of rare genetic variation on complex traits. However, there is a lack of knowledge on the impact of sample size, case numbers, the balance of cases vs controls for both burden and dispersion based rare variant association methods. For example, Phenome-Wide Association Studies may have a wide range of case and control sample sizes across hundreds of diagnoses and traits, and with the application of statistical methods to rare variants, it is important to understand the strengths and limitations of the analyses.