Synergistic Gene-Gene Interactions in Common Complex Diseases

• Activity Number: 455
• Type: Topic Contributed
• Date/Time: Wednesday, August 1, 2012 : 8:30 AM to 10:20 AM
• Sponsor: Biometrics Section
• Author(s): Itsik Pe'er*+
• Companies: Columbia University
• Keywords: interaction ; genetics ; association ; gene x gene ; GWAS ; sequencing

Abstract

A synergistic interaction between two or more genes is when the co-occurrence of specific alleles of these genes bears a greater joint effect on phenotype than a simple addition of their individual effects would suggest. These interactions are unique by virtue of having natural biological interpretations. Synergistic interactions have been widely reported across multiple traits in eukaryotic, plant and animal models. Their prevalence in common traits in humans, however, is still an open question, as interaction effects are almost undetectable to single marker association tests like GWAS. Additionally, the straightforward solution of exhaustively searching for these interactions in genome-scale datasets faces issues of computational and multiple test correction due to the sheer size of the search-space.

Our work considers a standard and interpretable test for gene x gene interaction - the Gametic Phase Disequilibrium (GPD) test. We focus on how to overcome the computational burden of applying the GPD-test to genome-scale datasets. We will present a novel and powerful new statistical and algorithmic framework - Probably Approximately Complete (PAC) searching - which can scan pairs/