Improved imputation accuracy of rare and low-frequency variants using population-specific high-coverage WGS-based imputation reference panel
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ejhg201751.pdf
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Author(s)
Mitt, Mario
Kals, Mart
Pärn, Kalle
Ripatti, Samuli
Morris, Andrew P
Metspalu, Andres
Esko, Tõnu
Mägi, Reedik
Palta, Priit
Gabriel, Stacey
Date Issued
April 2017
Journal
European Journal of Human Genetics
Publisher
Nature Publishing Group
Citation
Mitt, Mario et al. “Improved Imputation Accuracy of Rare and Low-Frequency Variants Using Population-Specific High-Coverage WGS-Based Imputation Reference Panel.” European Journal of Human Genetics 25, 7 (April 2017): 869–876 © 2017 The Author(s)
Version
Final published version
Abstract
Genetic imputation is a cost-efficient way to improve the power and resolution of genome-wide association (GWA) studies. Current publicly accessible imputation reference panels accurately predict genotypes for common variants with minor allele frequency (MAF)≥5% and low-frequency variants (0.5≤MAF<5%) across diverse populations, but the imputation of rare variation (MAF<0.5%) is still rather limited. In the current study, we evaluate imputation accuracy achieved with reference panels from diverse populations with a population-specific high-coverage (30 ×) whole-genome sequencing (WGS) based reference panel, comprising of 2244 Estonian individuals (0.25% of adult Estonians). Although the Estonian-specific panel contains fewer haplotypes and variants, the imputation confidence and accuracy of imputed low-frequency and rare variants was significantly higher. The results indicate the utility of population-specific reference panels for human genetic studies.
MIT Department
Broad Institute of MIT and Harvard
Massachusetts Institute of Technology. Department of Biology
Terms of Use
Creative Commons Attribution-NonCommercial 4.0 International
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DOI of Published Version
https://doi.org/10.1038/EJHG.2017.51
