We have described a practical strategy for imputing genotypes from the large reference panels that are now emerging from sequencing efforts like the 1000 Genomes Project. These panels are regularly updated, both to incorporate newly sequenced individuals and to take advantage of improved methods for analyzing next-generation sequence data that can handle increasingly diverse variant types, including insertion/deletion polymorphisms and copy number variants. New reference datasets may provide significant benefits for disease studies, but imputing them into large-scale GWAS currently requires substantial computational resources. The pre-phasing strategy introduced here will allow investigators to routinely impute from these emerging reference panels at a reasonable computational cost and thereby enhance studies of complex disease genetics.
