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The gain in sample size, however, often comes with a loss in coherence of both genetic and environmental measures. Recently developed methods in statistical genetics allow harmonisation of the genetic data, e.through imputation of SNP data to a common reference panel. In contrast, the risk-profiling method requires individual level genetic and environmental measures in only the target sample with the GRPS constructed based on GWAS summary statistics from a larger independent discovery sample that is (most likely) ignorant of the environmental conditions.

In the risk-profiling framework, identification of true interaction effects largely depends on the prediction accuracy of the genetic and environmental factors.