Genotype imputation using the Positional Burrows Wheeler Transform

Genome-wide association studies (GWAS) typically use microarray technology to measure genotypes at several hundred thousand positions in the genome. However reference panels of genetic variation consist of haplotype data at 100 fold more positions in the genome. Genotype imputation makes genotype predictions at all the reference panel sites using the GWAS data. Reference panels are continuing to grow in size and this improves accuracy of the predictions, however methods need to be able to scale this increased size. We have developed a new version of the popular IMPUTE software than can handle reference panels with millions of haplotypes, and has better performance than other published approaches. A notable property of the new method is that it scales sub-linearly with reference panel size. Keeping the number of imputed markers constant, a 100 fold increase in reference panel size requires less than twice the computation time.