[en] Large-scale epistasis studies can give new clues to system-level genetic mechanisms and a better understanding of the underlying biology of human complex disease traits. Though many novel methods have been proposed to carry out such studies, so far only a few of them have demonstrated replicable results. Here, we propose a minimal protocol for genome-wide association interaction (GWAI) analysis to identify gene–gene interactions from large-scale genomic data. The different steps of the developed protocol are discussed and motivated, and encompass interaction screening in a hypothesis-free and hypothesisdriven manner. In particular, we examine a wide range of aspects related to epistasis discovery in the context of complex traits in humans, hereby giving practical recommendations for data quality control, variant selection or
prioritization strategies and analytic tools, replication and meta-analysis, biological validation of statistical findings and other related aspects. The minimal protocol provides
guidelines and attention points for anyone involved in GWAI analysis and aims to enhance the biological relevance of GWAI findings. At the same time, the protocol improves a better assessment of strengths and weaknesses of published GWAI methodologies.
Disciplines :
Génétique & processus génétiques
Auteur, co-auteur :
Gusareva, Elena ; Université de Liège - ULiège > Dép. d'électric., électron. et informat. (Inst.Montefiore) > Bioinformatique
Van Steen, Kristel ; Université de Liège - ULiège > Dép. d'électric., électron. et informat. (Inst.Montefiore) > Bioinformatique
Langue du document :
Anglais
Titre :
Practical aspects of genome-wide association interaction analysis.
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