SIBLINK

SIBLINK estimates identity-by-descent (IBD) sharing among affected sibling pairs to perform multipoint linkage analysis and localize disease-associated loci.

Key Features:

• Multipoint linkage analysis: Conducts multipoint affected-sibling-pair (ASP) linkage analysis to localize genetic loci associated with disease.
• IBD estimation from IBS: Infers IBD status from observed identity-by-state (IBS) using marker genotypes, allele frequencies, and chromosomal locations.
• LOD score calculation and maximization: Calculates logarithm of odds (LOD) scores and maximizes them across a grid of potential disease loci and corresponding IBD sharing vectors.
• Integration with Ordered Subsets Analysis (OSA): Supports conditional linkage analysis by using LOD scores from one chromosome as covariates for analysis of another to explore epistatic interactions.

Scientific Applications:

• Single-locus linkage detection: Identifies linkage evidence for single-locus associations with diseases using affected sibling pairs.
• Benchmark dataset analysis: Applied to the Genetic Analysis Workshop 14 (GAW14) dataset for multipoint ASP linkage analysis across multiple chromosome replicates.
• Exploration of epistasis: Enables investigation of two-locus interactions through conditional linkage analysis with Ordered Subsets Analysis (OSA).

Methodology:

Infer IBD from IBS using marker genotypes, allele frequencies, and chromosomal locations; compute LOD scores for candidate loci; maximize LOD scores across a grid of potential disease locations and IBD sharing vectors; optionally perform conditional linkage analysis by incorporating per-chromosome LOD scores as covariates in Ordered Subsets Analysis (OSA).