CCREL

CCREL performs case-control genetic association analysis accounting for relatedness among individuals by incorporating identity-by-descent (IBD) sharing into single-marker and haplotypic tests for SNPs and other biallelic markers.

Key Features:

• Handling Relatedness: Calculates individual-specific weights based on IBD sharing to account for genetic correlations within pedigrees.
• Composite Likelihood Construction: Constructs a composite likelihood from IBD-based weights and conducts likelihood ratio tests via iterative maximization.
• Single-marker and Haplotypic Tests: Performs association testing on single SNP markers and haplotypes using biallelic marker data.
• Chromosomal Applicability: Applies to both autosomal and X chromosome analyses.
• Handling Missing Data: Incorporates approaches that improve analysis robustness in the presence of missing genotype data.
• Scalability: Scales with pedigree size and complexity for analyses involving extensive familial data.

Scientific Applications:

• Disease Association Studies: Used to identify marker–disease associations in family-based studies, for example investigating type 2 diabetes with SNPs in the PPAR-gamma gene.
• Increased Analytical Power: Leverages related cases to increase power relative to population-based case analyses by exploiting higher disease-allele frequencies within pedigrees and using all available cases per pedigree.

Methodology:

Computational steps explicitly include calculating individual weights from IBD sharing, constructing a composite likelihood using those weights and iteratively maximizing it to perform likelihood ratio tests, and validating performance and assessing power using simulated data.