RT Journal Article
SR Electronic
T1 Fast and accurate long-range phasing in a UK Biobank cohort
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 028282
DO 10.1101/028282
A1 Po-Ru Loh
A1 Pier Francesco Palamara
A1 Alkes L Price
YR 2015
UL http://biorxiv.org/content/early/2015/12/18/028282.abstract
AB Recent work has leveraged the extensive genotyping of the Icelandic population to perform long-range phasing (LRP), enabling accurate imputation and association analysis of rare variants in target samples typed on genotyping arrays. Here, we develop a fast and accurate LRP method, Eagle, that extends this paradigm to populations with much smaller proportions of genotyped samples by harnessing long (>4cM) identical-by-descent (IBD) tracts shared among distantly related individuals. We applied Eagle to N=150K samples (0.2% of the British population) from the UK Biobank, and we determined that it is 1–2 orders of magnitude faster than existing methods while achieving similar or better phasing accuracy (switch error rate ≈0.3%, corresponding to perfect phase in most 10Mb segments). We also observed that when used within an imputation pipeline, Eagle pre-phasing improved downstream imputation accuracy compared to pre-phasing in batches using existing methods (as necessary to achieve comparable computational cost).