Improved Imputation Accuracy of Rare and Low-frequency Variants Using Population-specific High-coverage WGS-based Imputation Reference Panel

Overview

Journal Eur J Hum Genet

Specialty Genetics

Date 2017 Apr 13

PMID 28401899

Citations 112

Authors

Mario Mitt

Mart Kals

Kalle Parn

Stacey B Gabriel

Eric S Lander

Aarno Palotie

Samuli Ripatti

Andrew P Morris

Andres Metspalu

Tonu Esko

Reedik Magi

Priit Palta

Affiliations

Soon will be listed here.

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.

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