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

Eur J Hum Genet. 2017 Jun;25(7):869-876. doi: 10.1038/ejhg.2017.51. Epub 2017 Apr 12.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Female
  • Gene Frequency*
  • Genome, Human*
  • Genome-Wide Association Study / methods
  • Genome-Wide Association Study / standards*
  • Haplotypes
  • Humans
  • Male
  • Polymorphism, Single Nucleotide*
  • Reference Standards
  • Sequence Analysis, DNA / methods
  • Sequence Analysis, DNA / standards*