This study investigated the impact of appearance phenotype correlations on genetic appearance prediction in the exemplary case of three pigmentation traits.
Predicting appearance phenotypes from genotypes is relevant for various areas of human genetic research and applications such as genetic epidemiology, human history, anthropology, and particularly in forensics. Many appearance phenotypes, and thus their underlying genotypes, are highly correlated, with pigmentation traits serving as primary examples; however, all available genetic prediction models, including those for pigmentation traits currently used in forensic DNA phenotyping, ignore phenotype correlations. The current study used data for categorical eye, hair and skin color, as well as 41 DNA markers used in the recently established HIrisPlex-S system from 762 individuals with complete phenotype and genotype information. Based on these data, researchers performed genetic prediction modelling of eye, hair, and skin color via three different strategies, namely the established approach of predicting phenotypes solely based on genotypes while not considering phenotype correlations, and two novel approaches that considered phenotype correlations, either incorporating truly observed correlated phenotypes or DNA-predicted correlated phenotypes in addition to the DNA predictors. The study found that using truly observed correlated pigmentation phenotypes as additional predictors increased the DNA-based prediction accuracies for almost all eye, hair, and skin color categories, with the largest increase for intermediate eye color, brown hair color, dark to black skin color, and particularly for dark skin color. Outcomes of dedicated computer simulations suggest that this prediction accuracy increase is due to the additional genetic information that is implicitly provided by the truly observed correlated pigmentation phenotypes used, yet not covered by the DNA predictors applied. In contrast, considering DNA-predicted correlated pigmentation phenotypes as additional predictors did not improve the performance of the genetic prediction of eye, hair and skin color, which was in line with the results from the computer simulations. Hence, in practical applications of DNA-based appearance prediction where no phenotype knowledge is available, such as in forensic DNA phenotyping, it is not advised to use DNA-predicted correlated phenotypes as predictors in addition to the DNA predictors. This is not recommended for the pigmentation traits and the established pigmentation DNA predictors tested here. (publisher abstract modified)