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Genotype imputation is the process of predicting unobserved genotypes in a sample of individuals using a reference panel of haplotypes. Increasing reference panel size poses ever increasing computational challenges for imputation methods. Here we present IMPUTE5, a genotype imputation method that can scale to reference panels with millions of samples. It achieves fast and memory-efficient imputation by selecting haplotypes using the Positional Burrows Wheeler Transform (PBWT), which are used asdoi:10.1101/797944 fatcat:6fsnffyru5bwxauq7xi7lqfqui