Analyses and comparison of accuracy of different genotype imputation methods

PLoS One. 2008;3(10):e3551. doi: 10.1371/journal.pone.0003551. Epub 2008 Oct 29.


The power of genetic association analyses is often compromised by missing genotypic data which contributes to lack of significant findings, e.g., in in silico replication studies. One solution is to impute untyped SNPs from typed flanking markers, based on known linkage disequilibrium (LD) relationships. Several imputation methods are available and their usefulness in association studies has been demonstrated, but factors affecting their relative performance in accuracy have not been systematically investigated. Therefore, we investigated and compared the performance of five popular genotype imputation methods, MACH, IMPUTE, fastPHASE, PLINK and Beagle, to assess and compare the effects of factors that affect imputation accuracy rates (ARs). Our results showed that a stronger LD and a lower MAF for an untyped marker produced better ARs for all the five methods. We also observed that a greater number of haplotypes in the reference sample resulted in higher ARs for MACH, IMPUTE, PLINK and Beagle, but had little influence on the ARs for fastPHASE. In general, MACH and IMPUTE produced similar results and these two methods consistently outperformed fastPHASE, PLINK and Beagle. Our study is helpful in guiding application of imputation methods in association analyses when genotype data are missing.

Publication types

  • Comparative Study
  • Evaluation Study
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Computational Biology / methods*
  • Computer Simulation
  • Efficiency
  • Genome-Wide Association Study / methods*
  • Genotype
  • Humans
  • Linkage Disequilibrium
  • Polymorphism, Single Nucleotide
  • Sensitivity and Specificity
  • Software
  • Time Factors