Comparison of HapMap and 1000 genomes reference panels in a large-scale genome-wide association study
An increasing number of genome-wide association (GWA) studies are now using the higher resolution 1000 Genomes Project reference panel (1000G) for imputation, with the expectation that 1000G imputation will lead to the discovery of additional associated loci when compared to HapMap imputation. In or...
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| Hauptverfasser: | , , , |
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| Dokumenttyp: | Article (Journal) |
| Sprache: | Englisch |
| Veröffentlicht: |
January 20, 2017
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| In: |
PLOS ONE
Year: 2017, Jahrgang: 12, Heft: 1 |
| ISSN: | 1932-6203 |
| DOI: | 10.1371/journal.pone.0167742 |
| Online-Zugang: | Verlag, Volltext: http://dx.doi.org/10.1371/journal.pone.0167742 Verlag, Volltext: https://doi.org/10.1371/journal.pone.0167742 
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| Verfasserangaben: | Paul S. de Vries, Maria Sabater-Lleal, Daniel I. Chasman, Stella Trompet, Tarunveer S. Ahluwalia, Alexander Teumer, Marcus E. Kleber, Ming-Huei Chen, Jie Jin Wang, John R. Attia, Riccardo E. Marioni, Maristella Steri, Lu-Chen Weng, Rene Pool, Vera Grossmann, Jennifer A. Brody, Cristina Venturini, Toshiko Tanaka, Lynda M. Rose, Christopher Oldmeadow, Johanna Mazur, Saonli Basu, Mattias Frånberg, Qiong Yang, Symen Ligthart, Jouke J. Hottenga, Ann Rumley, Antonella Mulas, Anton J. M. de Craen, Anne Grotevendt, Kent D. Taylor, Graciela E. Delgado, Annette Kifley, Lorna M. Lopez, Tina L. Berentzen, Massimo Mangino, Stefania Bandinelli, Alanna C. Morrison, Anders Hamsten, Geoffrey Tofler, Moniek P. M. de Maat, Harmen H. M. Draisma, Gordon D. Lowe, Magdalena Zoledziewska, Naveed Sattar, Karl J. Lackner, Uwe Völker, Barbara McKnight, Jie Huang, Elizabeth G. Holliday, Mark A. McEvoy, John M. Starr, Pirro G. Hysi, Dena G. Hernandez, Weihua Guan, Fernando Rivadeneira, Wendy L. McArdle, P. Eline Slagboom, Tanja Zeller, Bruce M. Psaty, André G. Uitterlinden, Eco J. C. de Geus, David J. Stott, Harald Binder, Albert Hofman, Oscar H. Franco, Jerome I. Rotter, Luigi Ferrucci, Tim D. Spector, Ian J. Deary, Winfried März, Andreas Greinacher, Philipp S. Wild, Francesco Cucca, Dorret I. Boomsma, Hugh Watkins, Weihong Tang, Paul M. Ridker, Jan W. Jukema, Rodney J. Scott, Paul Mitchell, Torben Hansen, Christopher J. O'Donnell, Nicholas L. Smith, David P. Strachan, Abbas Dehghan |
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| 245 | 1 | 0 | |a Comparison of HapMap and 1000 genomes reference panels in a large-scale genome-wide association study |c Paul S. de Vries, Maria Sabater-Lleal, Daniel I. Chasman, Stella Trompet, Tarunveer S. Ahluwalia, Alexander Teumer, Marcus E. Kleber, Ming-Huei Chen, Jie Jin Wang, John R. Attia, Riccardo E. Marioni, Maristella Steri, Lu-Chen Weng, Rene Pool, Vera Grossmann, Jennifer A. Brody, Cristina Venturini, Toshiko Tanaka, Lynda M. Rose, Christopher Oldmeadow, Johanna Mazur, Saonli Basu, Mattias Frånberg, Qiong Yang, Symen Ligthart, Jouke J. Hottenga, Ann Rumley, Antonella Mulas, Anton J. M. de Craen, Anne Grotevendt, Kent D. Taylor, Graciela E. Delgado, Annette Kifley, Lorna M. Lopez, Tina L. Berentzen, Massimo Mangino, Stefania Bandinelli, Alanna C. Morrison, Anders Hamsten, Geoffrey Tofler, Moniek P. M. de Maat, Harmen H. M. Draisma, Gordon D. Lowe, Magdalena Zoledziewska, Naveed Sattar, Karl J. Lackner, Uwe Völker, Barbara McKnight, Jie Huang, Elizabeth G. Holliday, Mark A. McEvoy, John M. Starr, Pirro G. Hysi, Dena G. Hernandez, Weihua Guan, Fernando Rivadeneira, Wendy L. McArdle, P. Eline Slagboom, Tanja Zeller, Bruce M. Psaty, André G. Uitterlinden, Eco J. C. de Geus, David J. Stott, Harald Binder, Albert Hofman, Oscar H. Franco, Jerome I. Rotter, Luigi Ferrucci, Tim D. Spector, Ian J. Deary, Winfried März, Andreas Greinacher, Philipp S. Wild, Francesco Cucca, Dorret I. Boomsma, Hugh Watkins, Weihong Tang, Paul M. Ridker, Jan W. Jukema, Rodney J. Scott, Paul Mitchell, Torben Hansen, Christopher J. O'Donnell, Nicholas L. Smith, David P. Strachan, Abbas Dehghan |
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| 520 | |a An increasing number of genome-wide association (GWA) studies are now using the higher resolution 1000 Genomes Project reference panel (1000G) for imputation, with the expectation that 1000G imputation will lead to the discovery of additional associated loci when compared to HapMap imputation. In order to assess the improvement of 1000G over HapMap imputation in identifying associated loci, we compared the results of GWA studies of circulating fibrinogen based on the two reference panels. Using both HapMap and 1000G imputation we performed a meta-analysis of 22 studies comprising the same 91,953 individuals. We identified six additional signals using 1000G imputation, while 29 loci were associated using both HapMap and 1000G imputation. One locus identified using HapMap imputation was not significant using 1000G imputation. The genome-wide significance threshold of 5×10−8 is based on the number of independent statistical tests using HapMap imputation, and 1000G imputation may lead to further independent tests that should be corrected for. When using a stricter Bonferroni correction for the 1000G GWA study (P-value < 2.5×10−8), the number of loci significant only using HapMap imputation increased to 4 while the number of loci significant only using 1000G decreased to 5. In conclusion, 1000G imputation enabled the identification of 20% more loci than HapMap imputation, although the advantage of 1000G imputation became less clear when a stricter Bonferroni correction was used. More generally, our results provide insights that are applicable to the implementation of other dense reference panels that are under development. | ||
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