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, Patrick
Menelaou, Androniki
van Leeuwen, Elisabeth M.
Kanterakis, Alexandros
van Dijk, Freerk
Medina-Gomez, Carolina
Francioli, Laurent C.
Hottenga, Jouke Jan
Karssen, Lennart C.
Estrada, Karol
Kreiner-Moller, Eskil
Rivadeneira, Fernando
van Setten, Jessica
Gutierrez-Achury, Javier
Westra, Harm-Jan
Franke, Lude
van Enckevort, David
Dijkstra, Martijn
Byelas, Heorhiy
van Duijn, Cornelia M.
de Bakker, Paul I. W.
Wijmenga, Cisca
Swertz, Morris A.
Dokumenttyp: Artikel
Erscheinungsdatum: 2014
Reihe/Periodikum: Deelen , P , Menelaou , A , van Leeuwen , E M , Kanterakis , A , van Dijk , F , Medina-Gomez , C , Francioli , L C , Hottenga , J J , Karssen , L C , Estrada , K , Kreiner-Moller , E , Rivadeneira , F , van Setten , J , Gutierrez-Achury , J , Westra , H-J , Franke , L , van Enckevort , D , Dijkstra , M , Byelas , H , van Duijn , C M , de Bakker , P I W , Wijmenga , C , Swertz , M A & Genome Netherlands Consortium 2014 , ' Improved imputation quality of low-frequency and rare variants in European samples using the 'Genome of The Netherlands' ' , European Journal of Human Genetics , vol. 22 , no. 11 , pp. 1321-1326 . https://doi.org/10.1038/ejhg.2014.19
Schlagwörter: genotype imputation / GWAS / GoNL / rare variants / reference sets / reference panel / WIDE ASSOCIATION / DISEASE / COMMON / ARRAY / POWER / LOCI
Sprache: Englisch
Permalink: https://search.fid-benelux.de/Record/base-29190679
Datenquelle: BASE; Originalkatalog
Powered By: BASE
Link(s) : https://hdl.handle.net/11370/37f56443-13eb-4e8c-8fc5-eef8612f1316

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 also saw improved imputation accuracy for other European populations (in the British samples, r(2) improved from 0.58 to 0.65, and in the Italians from 0.43 to 0.47). A combined reference set comprising 1000G and GoNL improved the imputation of rare variants even further. The Italian samples benefitted the most from this combined reference (the mean r(2) increased from 0.47 to 0.50). We conclude that the creation of a large population-specific reference is advantageous for imputing rare variants and that a combined reference panel across multiple populations yields the best imputation results.