Because MZ twins share all alleles and DZ twins only on average half, epistatic models predict higher MZ/DZ concordance ratios. If a multigene combination is required, the MZ/DZ ratio is higher, and it is very high if a multilocus epistatic combination is required. The odds that DZ twins will inherit a combination of alleles is 0.5 raised to the power of the number of alleles involved in the combination, (0.5)n. Multiple combinations may lead to the same phenotype, but for multilocus interactions this is less likely to compensate for the problem of joint probability to produce exactly 2:1 and 4:1 MZ/DZ ratios, as are expected for single alleles acting dominantly or recessively acting on a dichotomous trait, or for multiple alleles additively contributing to a quantitative trait. The MZ/DZ ratio for autism appears to be as high as 50:1, indicating that epistasis is likely. However, the MZ/DZ twin concordance ratios for SUDs (Fig. 4) converge on 2:1, consistent with alleles of individual effect and with the genetic heterogeneity model.
