Imputation of non-genotyped individuals based on genotyped relatives: assessing the imputation accuracy of a real case scenario in dairy cattle

Background

Imputation of genotypes for ungenotyped individuals could enable the use of valuable phenotypes created before the genomic era in analyses that require genotypes. The objective of this study was to investigate the accuracy of imputation of non-genotyped individuals using genotype information from relatives.

Methods

Genotypes were simulated for all individuals in the pedigree of a real (historical) dataset of phenotyped dairy cows and with part of the pedigree genotyped. The software AlphaImpute was used for imputation in its standard settings but also without phasing, i.e. using basic inheritance rules and segregation analysis only. Different scenarios were evaluated i.e.: (1) the real data scenario, (2) addition of genotypes of sires and maternal grandsires of the ungenotyped individuals, and (3) addition of one, two, or four genotyped offspring of the ungenotyped individuals to the reference population.

Results

The imputation accuracy using AlphaImpute in its standard settings was lower than without phasing. Including genotypes of sires and maternal grandsires in the reference population improved imputation accuracy, i.e. the correlation of the true genotypes with the imputed genotype dosages, corrected for mean gene content, across all animals increased from 0.47 (real situation) to 0.60. Including one, two and four genotyped offspring increased the accuracy of imputation across all animals from 0.57 (no offspring) to 0.73, 0.82, and 0.92, respectively.

Conclusions

At present, the use of basic inheritance rules and segregation analysis appears to be the best imputation method for ungenotyped individuals. Comparison of our empirical animal-specific imputation accuracies to predictions based on selection index theory suggested that not correcting for mean gene content considerably overestimates the true accuracy. Imputation of ungenotyped individuals can help to include valuable phenotypes for genome-wide association studies or for genomic prediction, especially when the ungenotyped individuals have genotyped offspring.