Reference-based phasing using the Haplotype Reference Consortium panel.

Nat Genet
Authors
Abstract

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.

Year of Publication
2016
Journal
Nat Genet
Volume
48
Issue
11
Pages
1443-1448
Date Published
2016 Nov
ISSN
1546-1718
DOI
10.1038/ng.3679
PubMed ID
27694958
PubMed Central ID
PMC5096458
Links
Grant list
S10 RR028832 / RR / NCRR NIH HHS / United States
R01 HG006399 / HG / NHGRI NIH HHS / United States
F32 HG007805 / HG / NHGRI NIH HHS / United States
R01 HG007022 / HG / NHGRI NIH HHS / United States
R01 MH101244 / MH / NIMH NIH HHS / United States
R01 HL117626 / HL / NHLBI NIH HHS / United States
R01 EY022005 / EY / NEI NIH HHS / United States