Two-stage genome-wide search for epistasis with implementation to Recombinant Inbred Lines (RIL) populations

Pavel Goldstein, Abraham B. Korol, Anat Reiner-Benaim

Research output: Contribution to journalArticlepeer-review

Abstract

Principal Findings: Both epistasis detection power and heritability contributed by epistasis increased when using multi-trait complexes rather than single traits. Epistatic effects common to the eQTLs included in the complexes have higher chance of being identified by analysis of multi-trait complexes, particularly when epistatic effects on individual traits are small. Compared to direct testing for all potential epistatic effects, the hierarchical search was substantially more powerful in detecting epistasis, while controlling the FDR at the desired level. Association in functional roles within genomic regions was observed, supporting an initial screen for epistatic QTLs.

Objective and Methods: This paper proposes an inegrative two-stage genomewide search for pairwise epistasis on expression quantitative trait loci (eQTL). The traits are clustered into multi-trait complexes that account for correlations between them that may result from common epistasis effects. The search is done by first screening for epistatic regions and then using dense markers within the identified regions, resulting in substantial reduction in the number of tests for epistasis. The FDR is controlled using a hierarchical procedure that accounts for the search structure. Each combination of trait and marker-pair is tested using a model that accounts for both statistical and functional interpretations of epistasis and considers orthogonal effects, such that their contributions to heritability can be estimated individually.We examine the impact of using multi-trait complexes rather than single traits, and of using a hierarchical search for epistasis rather than skipping the initial screen for epistatic regions. We apply the proposed algorithm on Arabidopsis transcription data.

Original languageEnglish
Article numbere115680
JournalPLoS ONE
Volume9
Issue number12
DOIs
StatePublished - 23 Dec 2014

Bibliographical note

Publisher Copyright:
© 2014 Goldstein et al.

ASJC Scopus subject areas

  • General Biochemistry, Genetics and Molecular Biology
  • General Agricultural and Biological Sciences
  • General

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