Eigen-Epistasis for detecting Gene-Gene interactions - Archive ouverte HAL
Pré-Publication, Document De Travail Année : 2016

Eigen-Epistasis for detecting Gene-Gene interactions

Résumé

A large amount of research has been devoted to the detection and investigation of epistatic interactions in genome-wide association studies (GWASs). Most of the literature focuses on low-order interactions between single-nucleotide polymorphisms (SNPs) with significant main effects. In this paper we propose an original approach for detecting epistasis at the gene level, without systematically filtering on significant genes. We first compute interaction variables for each gene pair by finding its Eigen-Epistasis component, defined as the linear combination of Gene SNPs having the highest correlation with the phenotype. The selection of significant effects is done using a penalized regression method based on Group Lasso controlling the False Discovery Rate. The method is tested against two recent alternative proposals from the literature using synthetic data, and shows good performances in different settings. Using a genome-wide association study relating to ankylosing spondylitis we demonstrate the power of our approach by detecting new gene-gene interactions.
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Dates et versions

hal-01275624 , version 1 (17-02-2016)
hal-01275624 , version 2 (22-02-2016)
hal-01275624 , version 3 (11-05-2016)
hal-01275624 , version 4 (17-06-2016)
hal-01275624 , version 5 (16-11-2016)
hal-01275624 , version 6 (14-02-2017)

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Virginie Stanislas, Cyril Dalmasso, Christophe Ambroise. Eigen-Epistasis for detecting Gene-Gene interactions. 2016. ⟨hal-01275624v4⟩
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