Improved imputation accuracy of rare and low-frequency variants using population-specific high-coverage WGS-based imputation reference panel

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&l...

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Bibliographic Details
Published in:European journal of human genetics : EJHG Vol. 25; no. 7; pp. 869 - 876
Main Authors: Mitt, Mario, Kals, Mart, Pärn, Kalle, Gabriel, Stacey B, Lander, Eric S, Palotie, Aarno, Ripatti, Samuli, Morris, Andrew P, Metspalu, Andres, Esko, Tõnu, Mägi, Reedik, Palta, Priit
Format: Journal Article
Language:English
Published: England Nature Publishing Group 01.06.2017
Subjects:
Accuracy
Bioinformatics
Consortia
Female
Gene Frequency
Genetics
Genome, Human
Genome-Wide Association Study - methods
Genome-Wide Association Study - standards
Genomes
Genotype & phenotype
Genotypes
Haplotypes
Humans
Licenses
Male
Polymorphism, Single Nucleotide
Population
Reference Standards
Sequence Analysis, DNA - methods
Sequence Analysis, DNA - standards
Studies
United Kingdom > UK
United States > US
Finland
Estonia
ISSN:1018-4813, 1476-5438, 1476-5438
Online Access:Get full text
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Summary: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.
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These authors contributed equally to this work.
These authors jointly supervised this work.
ISSN:1018-4813
1476-5438
1476-5438
DOI:10.1038/ejhg.2017.51