Reference-based phasing using the Haplotype Reference Consortium panel

Journal article

Haplotype phasing is a fundamental problem in medical and population genetics. Phasing is generally performed via statistical phasing in a genotyped cohort, an approach that can yield 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 Burrows-Wheeler transform. We demonstrate that Eagle2 attains a ∼20× speedup and ∼10% increase in accuracy compared to reference-based phasing using SHAPEIT2. On European-ancestry samples, Eagle2 with the HRC panel achieves >2× 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.

Authors: Loh, P; Danecek, P; Palamara, P; Fuchsberger, C; A Reshef, Y

• Publication status: Published
• Peer review status: Peer reviewed
• Publisher: Springer Nature
• Journal: Nature Genetics
• Volume: 48
• Issue: 11
• Pages: 1443-1448
• Publication date: 2016-10-03
• Acceptance date: 2016-08-29
• DOI: 10.1038/ng.3679
• EISSN: 1546-1718
• ISSN: 1061-4036
• Pmid: 27694958
• Language: English
• Keywords: FFR