Improved imputation quality of low-frequency and rare variants in European samples using the 'Genome of the Netherlands'

Although genome-wide association studies (GWAS) have identified many common variants associated with complex traits, low-frequency and rare variants have not been interrogated in a comprehensive manner. Imputation from dense reference panels, such as the 1000 Genomes Project (1000G), enables testing of ungenotyped variants for association. Here we present the results of imputation using a large, new population-specific panel: the Genome of The Netherlands (GoNL). We benchmarked the performance of the 1000G and GoNL reference sets by comparing imputation genotypes with 'true' genotypes typed on... Mehr ...

Verfasser: Deelen, P. (Patrick)
Menelaou, A. (Androniki)
Leeuwen, E.M. (Elisa) van
Kanterakis, A. (Alexandros)
Dijk, F. (Freerk) van
Medina-Gomez, M.C. (Carolina)
Francioli, L.C. (Laurent)
Hottenga, J.J. (Jouke Jan)
Karssen, L.C. (Lennart)
Estrada Gil, K. (Karol)
Kreiner-Møller, E. (Eskil)
Rivadeneira Ramirez, F. (Fernando)
Setten, J. (Jessica) van
Gutierrez-Achury, J. (Javier)
Westra, H.J. (Harm-Jan)
Franke, L. (Lude)
Enckevort, D. (David) van
Dijkstra, M.K.
Byelas, H. (Heorhiy)
Duijn, C.M. (Cornelia) van
Bakker, P.I.W. (Paul) de
Wijmenga, C. (Cisca)
Swertz, M. (Morris)
Dokumenttyp: Artikel
Erscheinungsdatum: 2014
Schlagwörter: genotype imputation / GoNL / GWAS / rare variants / reference panel / reference sets
Sprache: Englisch
Permalink: https://search.fid-benelux.de/Record/base-29199549
Datenquelle: BASE; Originalkatalog
Powered By: BASE
Link(s) : http://repub.eur.nl/pub/81172

Although genome-wide association studies (GWAS) have identified many common variants associated with complex traits, low-frequency and rare variants have not been interrogated in a comprehensive manner. Imputation from dense reference panels, such as the 1000 Genomes Project (1000G), enables testing of ungenotyped variants for association. Here we present the results of imputation using a large, new population-specific panel: the Genome of The Netherlands (GoNL). We benchmarked the performance of the 1000G and GoNL reference sets by comparing imputation genotypes with 'true' genotypes typed on ImmunoChip in three European populations (Dutch, British, and Italian). GoNL showed significant improvement in the imputation quality for rare variants (MAF 0.05-0.5%) compared with 1000G. In Dutch samples, the mean observed Pearson correlation, r 2, increased from 0.61 to 0.71. We