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

Eur J Hum Genet
Authors
Keywords
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≤MAF5%) across diverse populations, but the imputation of rare variation (MAF0.5%) 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.

Year of Publication
2017
Journal
Eur J Hum Genet
Volume
25
Issue
7
Pages
869-876
Date Published
2017 06
ISSN
1476-5438
DOI
10.1038/ejhg.2017.51
PubMed ID
28401899
PubMed Central ID
PMC5520064
Links
Grant list
Wellcome Trust / United Kingdom
098017 / Wellcome Trust / United Kingdom
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