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

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Author
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-Møller, 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
Swertz, Morris A
Neerincx, Pieter B T
Pulit, Sara L
Elbers, Clara C
Francesco Palamara, Pier
Pe'er, Itsik
Abdellaoui, Abdel
Kloosterman, Wigard P
van Oven, Mannis
Vermaat, Martijn
Li, Mingkun
Laros, Jeroen F J
Stoneking, Mark
de Knijff, Peter
Kayser, Manfred
Veldink, Jan H
van den Berg, Leonard H
den Dunnen, Johan T
Amin, Najaf
van der Velde, K Joeri
Jan Hottenga, Jouke
Kattenberg, Mathijs
van Schaik, Barbera D C
Bot, Jan
Nijman, Isaäuc J
Mei, Hailiang
Koval, Vyacheslav
Ye, Kai
Lameijer, Eric-Wubbo
Moed, Matthijs H
Hehir-Kwa, Jayne Y
Handsaker, Robert E
Sunyaev, Shamil R
Sohail, Mashaal
Hormozdiari, Fereydoun
Marschall, Tobias
Marschall, Schönhuth
Guryev, Victor
de Bakker, Paul I W
Slagboom, P Eline
Beekman, Marian B
de Craen, Anton J M
Suchiman, H Eka D
Hofman, Albert
van Duijn, Cornelia
Boomsma, Dorret I
Willemsen, Gonneke
Wolffenbuttel, Bruce H
Platteel, Mathieu
Pitts, Steven J
Potluri, Shobha
Cox, David R
Li, Qibin
Li, Yingrui
Du, Yuanping
Chen, Ruoyan
Cao, Hongzhi
Li, Ning
Cao, Sujie
Wang, Jun
Bovenberg, Jasper A
committee, Steering
Wijmenga, Cisca
van Ommen, Gertjan B
Note: Order does not necessarily reflect citation order of authors.
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https://doi.org/10.1038/ejhg.2014.19Metadata
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Deelen, P., A. Menelaou, E. M. van Leeuwen, A. Kanterakis, F. van Dijk, C. Medina-Gomez, L. C. Francioli, et al. 2014. “Improved imputation quality of low-frequency and rare variants in European samples using the ‘Genome of The Netherlands'.” European Journal of Human Genetics 22 (11): 1321-1326. doi:10.1038/ejhg.2014.19. http://dx.doi.org/10.1038/ejhg.2014.19.Abstract
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, r2, increased from 0.61 to 0.71. We also saw improved imputation accuracy for other European populations (in the British samples, r2 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 r2 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.Other Sources
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4200431/pdf/Terms of Use
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