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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.
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Yang et al. (1999) studied this question.
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