PT - JOURNAL ARTICLE AU - Po-Ru Loh AU - Petr Danecek AU - Pier Francesco Palamara AU - Christian Fuchsberger AU - Yakir A Reshef AU - Hilary K Finucane AU - Sebastian Schoenherr AU - Lukas Forer AU - Shane McCarthy AU - Goncalo R Abecasis AU - Richard Durbin AU - Alkes L Price TI - Reference-based phasing using the Haplotype Reference Consortium panel AID - 10.1101/052308 DP - 2016 Jan 01 TA - bioRxiv PG - 052308 4099 - http://biorxiv.org/content/early/2016/07/07/052308.short 4100 - http://biorxiv.org/content/early/2016/07/07/052308.full AB - 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.