TY - JOUR
T1 - Comparison of HapMap and 1000 Genomes Reference Panels in a Large-Scale Genome-Wide Association Study.
JF - PLoS One
Y1 - 2017
A1 - de Vries, Paul S
A1 - Sabater-Lleal, Maria
A1 - Chasman, Daniel I
A1 - Trompet, Stella
A1 - Ahluwalia, Tarunveer S
A1 - Teumer, Alexander
A1 - Kleber, Marcus E
A1 - Chen, Ming-Huei
A1 - Wang, Jie Jin
A1 - Attia, John R
A1 - Marioni, Riccardo E
A1 - Steri, Maristella
A1 - Weng, Lu-Chen
A1 - Pool, Rene
A1 - Grossmann, Vera
A1 - Brody, Jennifer A
A1 - Venturini, Cristina
A1 - Tanaka, Toshiko
A1 - Rose, Lynda M
A1 - Oldmeadow, Christopher
A1 - Mazur, Johanna
A1 - Basu, Saonli
A1 - Frånberg, Mattias
A1 - Yang, Qiong
A1 - Ligthart, Symen
A1 - Hottenga, Jouke J
A1 - Rumley, Ann
A1 - Mulas, Antonella
A1 - de Craen, Anton J M
A1 - Grotevendt, Anne
A1 - Taylor, Kent D
A1 - Delgado, Graciela E
A1 - Kifley, Annette
A1 - Lopez, Lorna M
A1 - Berentzen, Tina L
A1 - Mangino, Massimo
A1 - Bandinelli, Stefania
A1 - Morrison, Alanna C
A1 - Hamsten, Anders
A1 - Tofler, Geoffrey
A1 - de Maat, Moniek P M
A1 - Draisma, Harmen H M
A1 - Lowe, Gordon D
A1 - Zoledziewska, Magdalena
A1 - Sattar, Naveed
A1 - Lackner, Karl J
A1 - Völker, Uwe
A1 - McKnight, Barbara
A1 - Huang, Jie
A1 - Holliday, Elizabeth G
A1 - McEvoy, Mark A
A1 - Starr, John M
A1 - Hysi, Pirro G
A1 - Hernandez, Dena G
A1 - Guan, Weihua
A1 - Rivadeneira, Fernando
A1 - McArdle, Wendy L
A1 - Slagboom, P Eline
A1 - Zeller, Tanja
A1 - Psaty, Bruce M
A1 - Uitterlinden, André G
A1 - de Geus, Eco J C
A1 - Stott, David J
A1 - Binder, Harald
A1 - Hofman, Albert
A1 - Franco, Oscar H
A1 - Rotter, Jerome I
A1 - Ferrucci, Luigi
A1 - Spector, Tim D
A1 - Deary, Ian J
A1 - März, Winfried
A1 - Greinacher, Andreas
A1 - Wild, Philipp S
A1 - Cucca, Francesco
A1 - Boomsma, Dorret I
A1 - Watkins, Hugh
A1 - Tang, Weihong
A1 - Ridker, Paul M
A1 - Jukema, Jan W
A1 - Scott, Rodney J
A1 - Mitchell, Paul
A1 - Hansen, Torben
A1 - O'Donnell, Christopher J
A1 - Smith, Nicholas L
A1 - Strachan, David P
A1 - Dehghan, Abbas
AB - 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.

VL - 12
IS - 1
ER -