%0 Journal Article %A Po-Ru Loh %A Petr Danecek %A Pier Francesco Palamara %A Christian Fuchsberger %A Yakir A Reshef %A Hilary K Finucane %A Sebastian Schoenherr %A Lukas Forer %A Shane McCarthy %A Goncalo R Abecasis %A Richard Durbin %A Alkes L Price %T Reference-based phasing using the Haplotype Reference Consortium panel %D 2016 %R 10.1101/052308 %J bioRxiv %P 052308 %X Haplotype phasing is a fundamental problem in medical and population genetics. Phasing is generally performed via statistical phasing within a genotyped cohort, an approach that can attain high accuracy in very large cohorts but attains lower accuracy in smaller cohorts. Here, we instead explore the paradigm of reference-based phasing. We introduce a new phasing algorithm, Eagle2, that attains high accuracy across a broad range of cohort sizes by efficiently leveraging information from large external reference panels (such as the Haplotype Reference Consortium, HRC) using a new data structure based on the positional BurrowsWheeler transform. We demonstrate that Eagle2 attains a ≈20x speedup and ≈10% increase in accuracy compared to reference-based phasing using SHAPEIT2. On European-ancestry samples, Eagle2 with the HRC panel achieves >2x the accuracy of 1000 Genomes-based phasing. Eagle2 is open source and freely available for HRC-based phasing via the Sanger Imputation Service and the Michigan Imputation Server. %U https://www.biorxiv.org/content/biorxiv/early/2016/07/07/052308.full.pdf