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

Year: 2017

Type: article

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.

Source: European Journal of Human Genetics

DOI: 10.1038/ejhg.2017.51

Authors: Mario Mitt, Mart Kals, Kalle Pärn, Stacey B Gabriel, Eric S Lander, Aarno Palotie, Samuli Ripatti, Andrew P Morris, Andres Metspalu, Tõnu Esko, Reedik Mägi, Priit Palta

Institutions: University of Tartu, University of Helsinki, Institute for Molecular Medicine Finland, Broad Institute, University of Liverpool

Language: English

Topic: Genetic Associations and Epidemiology

Subfield: Genetics

Field: Biochemistry, Genetics and Molecular Biology

Domain: Life Sciences

SDG: Good health and well-being

Open Access status: hybrid

Estimated APC paid: $2,790

Funders: Wellcome Trust, Netherlands eScience Center, European Commission, Eesti Teadusagentuur, NordForsk, Tartu Ülikool, Horizon 2020 Framework Programme, European Regional Development Fund

OpenAlex ID: W2605706957