GxGscan

GxGscan detects gene-gene (G × G) interactions in genome-wide association studies (GWAS) to improve identification of interacting single nucleotide polymorphisms (SNPs) despite small marginal effects and stringent multiple-testing corrections.

Key Features:

• Two-Step Procedure: An initial screening evaluates all SNP pairs in the combined sample of cases and controls and pairs that pass screening undergo a traditional G × G interaction test.
• Increased Detection Power: With 2,000 cases and 2,000 controls, GxGscan achieves over 90% power to detect an interaction odds ratio of 2.0, compared with less than 50% for traditional exhaustive pairwise testing.
• Hybrid Approach: Incorporates a hybrid two-step method that combines the proposed procedure with existing tests for marginal effects to retain favorable power properties from both approaches.
• Computational Feasibility: Validated on large-scale data, including application to an asthma GWAS from the University of Southern California Children's Health Study, demonstrating practical G × G scan performance on large datasets.

Scientific Applications:

• Detection of epistatic interactions: Identifies SNP pairs exhibiting G × G interactions that may be missed by single-SNP analyses.
• Complementing single-SNP GWAS: Provides follow-up analysis to uncover interaction-driven signals not captured by marginal-effect tests.
• Analysis of complex trait architectures: Enables investigation of how interacting loci contribute to the genetic architecture of traits and diseases.

Methodology:

All SNP pairs are initially screened for associations in the combined dataset of cases and controls, selected pairs are subjected to traditional G × G interaction tests, and the approach can be executed as a hybrid that integrates existing marginal-effect tests.