RRIntCC

RRIntCC detects region-region interactions in genome-wide case-control studies by leveraging correlations among SNP-SNP interactions via the linkage disequilibrium (LD) contrast test to identify region-level epistatic associations.

Key Features:

• Region-based interaction detection: Aggregates information from individual SNP-SNP interactions to analyze interactions at the genomic region level rather than only at single SNP pairs.
• Linkage disequilibrium (LD) contrast test: Utilizes the LD contrast test to leverage correlations between individual SNP-SNP interactions for region-level inference.
• Correlation-based aggregation: Exploits correlations among SNP-SNP interaction signals to improve detection of region-region interactions.
• Statistical performance: Simulation experiments indicate higher statistical power while maintaining similar type-I-error rates compared to SNP-based methods.
• Comparison to SNP-based methods: Demonstrated superior performance relative to traditional SNP-SNP interaction approaches and identified significant regions not detected by BOOST; comparisons include PLINK.
• Marginal effects extension: Extends analysis of marginal SNP effects to the regional level, enabling assessment of single-SNP impacts within regional interaction contexts.
• Validation on real data: Applied to real datasets where it discovered significant regions missed by conventional SNP-based methods.

Scientific Applications:

• GWAS case-control studies: Mapping region-region interactions in genome-wide association case-control datasets.
• Epistatic association discovery: Identifying region-level epistatic associations contributing to complex traits and diseases.
• Complementary analysis to SNP scans: Complementing SNP-SNP interaction scans (e.g., BOOST, PLINK) to reveal additional region-level associations.
• Marginal effect analysis at region scale: Assessing marginal SNP effects within a regional interaction framework to better capture functional units underlying phenotypes.

Methodology:

Aggregates SNP-SNP interaction correlations across genomic regions and applies the linkage disequilibrium (LD) contrast test to detect region-region interactions.