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/2016/05/10/052308.short
4100  - http://biorxiv.org/content/early/2016/05/10/052308.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 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 Burrows-Wheeler transform. Our method improves phasing accuracy by >2x compared to the best publicly available alternative for phasing small European-ancestry cohorts, and it attains a ≈20x speedup and ≈10% increase in accuracy compared to reference-based phasing using SHAPEIT2. Our method is freely available for reference-based phasing using the HRC panel via the Sanger Imputation Service and the Michigan Imputation Server.