The impact of imputation on meta-analysis of genome-wide association studies

PLoS One. 2012;7(4):e34486. doi: 10.1371/journal.pone.0034486. Epub 2012 Apr 5.

Abstract

Genotype imputation is often used in the meta-analysis of genome-wide association studies (GWAS), for combining data from different studies and/or genotyping platforms, in order to improve the ability for detecting disease variants with small to moderate effects. However, how genotype imputation affects the performance of the meta-analysis of GWAS is largely unknown. In this study, we investigated the effects of genotype imputation on the performance of meta-analysis through simulations based on empirical data from the Framingham Heart Study. We found that when fix-effects models were used, considerable between-study heterogeneity was detected when causal variants were typed in only some but not all individual studies, resulting in up to ∼25% reduction of detection power. For certain situations, the power of the meta-analysis can be even less than that of individual studies. Additional analyses showed that the detection power was slightly improved when between-study heterogeneity was partially controlled through the random-effects model, relative to that of the fixed-effects model. Our study may aid in the planning, data analysis, and interpretation of GWAS meta-analysis results when genotype imputation is necessary.

Publication types

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

MeSH terms

  • Cardiovascular Diseases / genetics*
  • Computer Simulation
  • Genome, Human
  • Genome-Wide Association Study*
  • Genotype*
  • Humans
  • Meta-Analysis as Topic
  • Models, Genetic*
  • Models, Statistical*
  • Phenotype
  • Polymorphism, Single Nucleotide / genetics*