title: Improved imputation accuracy of rare and low-frequency variants using population-specific high-coverage WGS-based imputation reference panel.
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.
authors.affiliation: Estonian Genome Center, University of Tartu, Tartu, Estonia.|Department of Biotechnology, Institute of Molecular and Cell Biology, University of Tartu, Tartu, Estonia.
authors.forename: Mario
authors.initials: M
authors.lastname: Mitt
authors.affiliation: Estonian Genome Center, University of Tartu, Tartu, Estonia.|Institute of Mathematics and Statistics, University of Tartu, Tartu, Estonia.
authors.forename: Mart
authors.initials: M
authors.lastname: Kals
authors.affiliation: Estonian Genome Center, University of Tartu, Tartu, Estonia.|Institute for Molecular Medicine Finland (FIMM), University of Helsinki, Helsinki, Finland.
authors.forename: Kalle
authors.initials: K
authors.lastname: Pärn
authors.affiliation: Broad Institute of MIT and Harvard, Cambridge, Massachusetts, USA.
authors.forename: Stacey B
authors.initials: SB
authors.lastname: Gabriel
authors.affiliation: Broad Institute of MIT and Harvard, Cambridge, Massachusetts, USA.
authors.forename: Eric S
authors.initials: ES
authors.lastname: Lander
authors.affiliation: Institute for Molecular Medicine Finland (FIMM), University of Helsinki, Helsinki, Finland.|Broad Institute of MIT and Harvard, Cambridge, Massachusetts, USA.
authors.forename: Aarno
authors.initials: A
authors.lastname: Palotie
authors.affiliation: Institute for Molecular Medicine Finland (FIMM), University of Helsinki, Helsinki, Finland.
authors.forename: Samuli
authors.initials: S
authors.lastname: Ripatti
authors.affiliation: Estonian Genome Center, University of Tartu, Tartu, Estonia.|Department of Biostatistics, University of Liverpool, Liverpool, UK.
authors.forename: Andrew P
authors.initials: AP
authors.lastname: Morris
authors.affiliation: Estonian Genome Center, University of Tartu, Tartu, Estonia.|Department of Biotechnology, Institute of Molecular and Cell Biology, University of Tartu, Tartu, Estonia.
authors.forename: Andres
authors.initials: A
authors.lastname: Metspalu
authors.affiliation: Estonian Genome Center, University of Tartu, Tartu, Estonia.|Broad Institute of MIT and Harvard, Cambridge, Massachusetts, USA.
authors.forename: Tõnu
authors.initials: T
authors.lastname: Esko
authors.affiliation: Estonian Genome Center, University of Tartu, Tartu, Estonia.
authors.forename: Reedik
authors.initials: R
authors.lastname: Mägi
authors.affiliation: Estonian Genome Center, University of Tartu, Tartu, Estonia.|Institute for Molecular Medicine Finland (FIMM), University of Helsinki, Helsinki, Finland.
authors.forename: Priit
authors.initials: P
authors.lastname: Palta
mesh_terms: D005260:Female; D005787:Gene Frequency; D015894:Genome, Human; D055106:Genome-Wide Association Study / Q000379:methods / Q000592:standards*; D006239:Haplotypes; D006801:Humans; D008297:Male; D020641:Polymorphism, Single Nucleotide; D012015:Reference Standards; D017422:Sequence Analysis, DNA / Q000379:methods / Q000592:standards*