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heritability of the disease in the two environments) is problematic, exacerbated by potentially different lifetime disease prevalences under the two environmental conditions, which may be unknown or difficult to estimate. A magnitude of the interaction variance can be estimated in the univariate mixed linear model. Application of the mixed model method requires data sets in which all individuals are measured for genome-wide genotypes and the environmental risk factor.

The mixed linear model method requires large samples measured for both individual level genetic and environmental measures (based on power considerations (e.Dudbridge, 2013; Visscher et al.