Analyses and comparison of imputation-based association methods

PLoS One. 2010 May 26;5(5):e10827. doi: 10.1371/journal.pone.0010827.


Genotype imputation methods have become increasingly popular for recovering untyped genotype data. An important application with imputed genotypes is to test genetic association for diseases. Imputation-based association test can provide additional insight beyond what is provided by testing on typed tagging SNPs only. A variety of effective imputation-based association tests have been proposed. However, their performances are affected by a variety of genetic factors, which have not been well studied. In this study, using both simulated and real data sets, we investigated the effects of LD, MAF of untyped causal SNP and imputation accuracy rate on the performances of seven popular imputation-based association methods, including MACH2qtl/dat, SNPTEST, ProbABEL, Beagle, Plink, BIMBAM and SNPMStat. We also aimed to provide a comprehensive comparison among methods. Results show that: 1). imputation-based association tests can boost signals and improve power under medium and high LD levels, with the power improvement increasing with strengthening LD level; 2) the power increases with higher MAF of untyped causal SNPs under medium to high LD level; 3). under low LD level, a high imputation accuracy rate cannot guarantee an improvement of power; 4). among methods, MACH2qtl/dat, ProbABEL and SNPTEST perform similarly and they consistently outperform other methods. Our results are helpful in guiding the choice of imputation-based association test in practical application.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Computational Biology / methods*
  • Databases, Genetic
  • Gene Frequency / genetics
  • Genome-Wide Association Study / methods*
  • Humans
  • Linkage Disequilibrium / genetics
  • Polymorphism, Single Nucleotide / genetics
  • Predictive Value of Tests
  • Quantitative Trait, Heritable
  • Time Factors