The case-only design is a powerful approach to detect interactions but should be used with caution

We determined the upper bound of the disease prevalence in order not to violate the rare disease assumption for the case-only design. To verify that a case-only design study does not have increased type I error rate, the bias of the interaction term should be estimated. Although the case-only design is a powerful method to detect interactions, prevalences for some complex traits are too high to implement this method without increasing type I error rates.