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 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 91,9... Mehr ...

Verfasser: de Vries, Paul S
Sabater-Lleal, Maria
Chasman, Daniel I
Trompet, Stella
Ahluwalia, Tarunveer S
Teumer, Alexander
Kleber, Marcus E
Chen, Ming-Huei
Wang, Jie Jin
Attia, John R
Marioni, Riccardo E
Steri, Maristella
Weng, Lu-Chen
Pool, Rene
Grossmann, Vera
Brody, Jennifer A
Venturini, Cristina
Tanaka, Toshiko
Rose, Lynda M
Oldmeadow, Christopher
Mazur, Johanna
Basu, Saonli
Frånberg, Mattias
Yang, Qiong
Ligthart, Symen
Hottenga, Jouke J
Rumley, Ann
Mulas, Antonella
De Craen, Anton J M
Grotevendt, Anne
Taylor, Kent D
Delgado, Graciela E
Kifley, Annette
Lopez, Lorna M
Berentzen, Tina L
Mangino, Massimo
Bandinelli, Stefania
Morrison, Alanna C
Hamsten, Anders
Tofler, Geoffrey
de Maat, Moniek P M
Draisma, Harmen H M
Lowe, Gordon D
Zoledziewska, Magdalena
Sattar, Naveed
Lackner, Karl J
Völker, Uwe
McKnight, Barbara
Huang, Jie
Holliday, Elizabeth G
McEvoy, Mark A
Starr, John M
Hysi, Pirro G
Hernandez, Dena G
Guan, Weihua
Rivadeneira, Fernando
McArdle, Wendy L
Slagboom, P. Eline
Zeller, Tanja
Psaty, Bruce M
Uitterlinden, André G
de Geus, Eco J C
Stott, David J
Binder, Harald
Hofman, Albert
Franco, Oscar H
Rotter, Jerome I
Ferrucci, Luigi
Spector, Tim D
Deary, Ian J
März, Winfried
Greinacher, Andreas
Wild, Philipp S
Cucca, Francesco
Boomsma, Dorret I
Watkins, Hugh
Tang, Weihong
Ridker, Paul M
Jukema, Jan W
Scott, Rodney J
Mitchell, Paul
Hansen, Torben
O'Donnell, Christopher J
Smith, Nicholas L
Strachan, David P
Dehghan, Abbas
Dokumenttyp: Artikel
Erscheinungsdatum: 2017
Reihe/Periodikum: de Vries , P S , Sabater-Lleal , M , Chasman , D I , Trompet , S , Ahluwalia , T S , Teumer , A , Kleber , M E , Chen , M-H , Wang , J J , Attia , J R , Marioni , R E , Steri , M , Weng , L-C , Pool , R , Grossmann , V , Brody , J A , Venturini , C , Tanaka , T , Rose , L M , Oldmeadow , C , Mazur , J , Basu , S , Frånberg , M , Yang , Q , Ligthart , S , Hottenga , J J , Rumley , A , Mulas , A , De Craen , A J M , Grotevendt , A , Taylor , K D , Delgado , G E , Kifley , A , Lopez , L M , Berentzen , T L , Mangino , M , Bandinelli , S , Morrison , A C , Hamsten , A , Tofler , G , de Maat , M P M , Draisma , H H M , Lowe , G D , Zoledziewska , M , Sattar , N , Lackner , K J , Völker , U , McKnight , B , Huang , J , Holliday , E G , McEvoy , M A , Starr , J M , Hysi , P G , Hernandez , D G , Guan , W , Rivadeneira , F , McArdle , W L , Slagboom , P E , Zeller , T , Psaty , B M , Uitterlinden , A G , de Geus , E J C , Stott , D J , Binder , H , Hofman , A , Franco , O H , Rotter , J I , Ferrucci , L , Spector , T D , Deary , I J , März , W , Greinacher , A , Wild , P S , Cucca , F , Boomsma , D I , Watkins , H , Tang , W , Ridker , P M , Jukema , J W , Scott , R J , Mitchell , P , Hansen , T , O'Donnell , C J , Smith , N L , Strachan , D P & Dehghan , A 2017 , ' Comparison of HapMap and 1000 Genomes Reference Panels in a Large-Scale Genome-Wide Association Study ' , PLoS ONE , vol. 12 , no. 1 , e0167742 , pp. e0167742 . https://doi.org/10.1371/journal.pone.0167742
Schlagwörter: Journal Article / /dk/atira/pure/keywords/cohort_studies/netherlands_twin_register_ntr_ / name=Netherlands Twin Register (NTR)
Sprache: Englisch
Permalink: https://search.fid-benelux.de/Record/base-29213854
Datenquelle: BASE; Originalkatalog
Powered By: BASE
Link(s) : https://research.vu.nl/en/publications/5d116b0a-bf29-4078-bcc0-8abd5e043627

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.