Epistasis: Obstacle or Advantage for Mapping Complex Traits?

K.J.F. Verhoeven, G. Casella, L.M. McIntyre

Research output: Contribution to journalArticleAcademicpeer-review

10 Citations (Scopus)

Abstract

Identification of genetic loci in complex traits has focused largely on one-dimensional genome scans to search for associations between single markers and the phenotype. There is mounting evidence that locus interactions, or epistasis, are a crucial component of the genetic architecture of biologically relevant traits. However, epistasis is often viewed as a nuisance factor that reduces power for locus detection. Counter to expectations, recent work shows that fitting full models, instead of testing marker main effect and interaction components separately, in exhaustive multi-locus genome scans can have higher power to detect loci when epistasis is present than single-locus scans, and improvement that comes despite a much larger multiple testing alpha-adjustment in such searches. We demonstrate, both theoretically and via simulation, that the expected power to detect loci when fitting full models is often larger when these loci act epistatically than when they act additively. Additionally, we show that the power for single locus detection may be improved in cases of epistasis compared to the additive model. Our exploration of a two step model selection procedure shows that identifying the true model is difficult. However, this difficulty is certainly not exacerbated by the presence of epistasis, on the contrary, in some cases the presence of epistasis can aid in model selection. The impact of allele frequencies on both power and model selection is dramatic.
Original languageEnglish
Article numbere12264
Number of pages12
JournalPLoS ONE
Volume5
DOIs
Publication statusPublished - 2010

Keywords

  • genome-wide association
  • linkage disequilibrium
  • genetic architecture
  • multiple loci
  • arabidopsis-thaliana
  • quantitative traits
  • flanking markers
  • model selection
  • high-resolution
  • snp discovery

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    Verhoeven, K. J. F., Casella, G., & McIntyre, L. M. (2010). Epistasis: Obstacle or Advantage for Mapping Complex Traits? PLoS ONE, 5, [e12264]. https://doi.org/10.1371/journal.pone.0012264