Methods of genotype imputation for genome-wide association studies

In genetic epidemiological studies, missing data problems arise when genotypes of particular markers are unavailable for reasons of data quality, cost efficiency or technical design. Genotype imputation is a well-established statistical technique for estimating unobserved genotypes in association studies. Imputation methods are implemented by copying haplotype segments from a densely genotyped reference panel into individuals typed at a subset of the reference variants. By this way, genotypes can be estimated and tested for association at variants that were not assayed in a study. This report first summarizes the missing data mechanisms. Then an overview of the different methods that have been proposed for genotype imputation is provided and some thoughts for future directions are given.