SIXPAC

SIXPAC identifies long-range gene–gene interactions by contrasting linkage disequilibrium patterns between single-nucleotide polymorphisms (SNPs) in case–control datasets to map interactions relevant to complex diseases.

Key Features:

• Novel algorithmic approach: Contrasts linkage disequilibrium between SNPs in case–control datasets using a standard two-locus test to detect long-range interactions.
• Randomization-based acceleration: Implements a randomization technique that requires 10 to 100 times fewer tests than brute-force methods, enabling ultrafast genome-wide scans.
• Efficient data handling: Processes datasets with thousands of cases and controls and hundreds of thousands of SNPs within hours.
• Statistical rigor via sampling: Samples small groups of cases and focuses on allele combinations present across these groups to narrow the search space while retaining identification of statistically significant SNP pairs.

Scientific Applications:

• Complex disease interaction mapping: Maps long-range SNP–SNP interactions to elucidate genetic architecture and pathways in complex diseases.
• Discovery and replication in psychiatric genetics: Applied to bipolar disorder datasets, identifying an interaction between SNPs in RYR2 and CACNA2D4 that replicated in an independent GAIN dataset.

Methodology:

Contrasts linkage disequilibrium between SNPs in cases versus controls using a standard two-locus test, applies a randomization technique, and samples small groups of cases focusing on allele combinations present across these groups.