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Comparison of HapMap and 1000 Genomes Reference Panels in a Large-Scale Genome-Wide Association Study

de Vries, PS; Sabater-Lleal, M; Chasman, DI; Trompet, S; Ahluwalia, TS; Teumer, A; Kleber, ME; ... Dehghan, A; + view all (2017) Comparison of HapMap and 1000 Genomes Reference Panels in a Large-Scale Genome-Wide Association Study. PLoS ONE , 12 (1) , Article e0167742. 10.1371/journal.pone.0167742. Green open access

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Abstract

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.

Type: Article
Title: Comparison of HapMap and 1000 Genomes Reference Panels in a Large-Scale Genome-Wide Association Study
Open access status: An open access version is available from UCL Discovery
DOI: 10.1371/journal.pone.0167742
Publisher version: http://dx.doi.org/10.1371/journal.pone.0167742
Language: English
Additional information: This is an open access article, free of all copyright, and may be freely reproduced, distributed, transmi tted, modifie d, built upon, or otherwise used by anyone for any lawful purpose. The work is made available under the Creative Commons CC0 public domain dedication.
Keywords: Science & Technology, Multidisciplinary Sciences, Science & Technology - Other Topics, Cardiovascular-Disease, Susceptibility Loci, Genetic-Variants, Common Variants, Metaanalysis, Consortium, Imputation, Pressure, Insights, Biology
UCL classification: UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > UCL GOS Institute of Child Health
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > UCL GOS Institute of Child Health > Infection, Immunity and Inflammation Dept
URI: https://discovery.ucl.ac.uk/id/eprint/1542472
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