Case only design to measure gene-gene interaction

The case-only design is an efficient and valid approach to screening for gene-environment interaction under the assumption of the independence between exposure and genotype in the population. In this paper, we show that the case-only design is also a valid and efficient approach to measuring gene-gene interaction under the assumption that the frequencies of genes are independent in the population. Just as the case only design requires fewer cases than the case-control design to measure gene environment interaction, it also requires fewer cases to measure gene-gene interactions.