Genotype imputation can be implemented with MapReduce, as the computationally expensive whole-genome calculations can be split into independent chromosome segments. Our imputation server accepts phased and unphased GWAS genotypes in VCF file format. File format checks and initial statistics (numbers of individuals and SNVs, detected chromosomes, unphased/phased data set, and number of chunks) are generated during the preprocessing step. Then, the submitted genotypes are compared to the reference panel to ensure that alleles, allele frequencies, strand orientation, and variant coding are correct. In this first MapReduce analysis, the map function calculates the VCF statistics for each file chunk, and the reducer summarizes the results and forwards only chunks that pass quality control to the subsequent imputation step (Supplementary Fig. 2). The MapReduce imputation step constitutes a map-only job. This means that no reducer is applied and each mapper imputes genotypes using minimac3 on the previously generated chunk. If the user has uploaded unphased genotypes, the data are prephased with one of the available phasing engines: Eagle 2, HAPI-UR34, or SHAPEIT17. A post-processing step generates a zipped and indexed VCF file
