title: Analysis pipeline for the epistasis search - statistical versus biological filtering.
abstract: Gene-gene interactions may contribute to the genetic variation underlying complex traits but have not always been taken fully into account. Statistical analyses that consider gene-gene interaction may increase the power of detecting associations, especially for low-marginal-effect markers, and may explain in part the "missing heritability." Detecting pair-wise and higher-order interactions genome-wide requires enormous computational power. Filtering pipelines increase the computational speed by limiting the number of tests performed. We summarize existing filtering approaches to detect epistasis, after distinguishing the purposes that lead us to search for epistasis. Statistical filtering includes quality control on the basis of single marker statistics to avoid the analysis of bad and least informative data, and limits the search space for finding interactions. Biological filtering includes targeting specific pathways, integrating various databases based on known biological and metabolic pathways, gene function ontology and protein-protein interactions. It is increasingly possible to target single-nucleotide polymorphisms that have defined functions on gene expression, though not belonging to protein-coding genes. Filtering can improve the power of an interaction association study, but also increases the chance of missing important findings.
authors.affiliation: Department of Epidemiology and Biostatistics, Case Western Reserve University Cleveland, OH, USA.
authors.forename: Xiangqing
authors.initials: X
authors.lastname: Sun
authors.affiliation: Department of Epidemiology and Biostatistics, Michigan State University East Lansing, MI, USA.
authors.forename: Qing
authors.initials: Q
authors.lastname: Lu
authors.affiliation: Department of Medicine, University of Washington Seattle, WA, USA.
authors.forename: Shubhabrata
authors.initials: S
authors.lastname: Mukherjee
authors.forename: Shubhabrata
authors.initials: S
authors.lastname: Mukheerjee
authors.affiliation: Department of Medicine, University of Washington Seattle, WA, USA.
authors.forename: Paul K
authors.initials: PK
authors.lastname: Crane
authors.affiliation: Department of Epidemiology and Biostatistics, Case Western Reserve University Cleveland, OH, USA.
authors.forename: Robert
authors.initials: R
authors.lastname: Elston
authors.affiliation: Department of Biochemistry and Molecular Biology, The Pennsylvania State University, University Park PA, USA.
authors.forename: Marylyn D
authors.initials: MD
authors.lastname: Ritchie
keywords: biological interaction; epistasis; filtering pipeline; genetic interaction; optimal search