TriadSim

TriadSim simulates autosomal genotypes preserving realistic linkage disequilibrium structures and incorporating user-specified genetic effects to generate data for evaluation of case-parent triads, case-control, case-only, and quantitative-trait genetic association studies.

Key Features:

• Realistic Linkage Disequilibrium: Uses existing genome-wide association data from unrelated case-parent triads to maintain realistic LD patterns in simulated genotypes.
• Spiked-In Genetic Effects: Allows specification of single- or multi-SNP causal effects, including epistasis (interactions between specific SNPs at defined loci or "pathways").
• Supported Study Designs: Generates data appropriate for case-parent triads, case-control studies, case-only studies, and quantitative-trait analyses.
• Probabilistic Trait Assignment: Assigns qualitative or quantitative offspring traits based on user-defined risk models to control trait status in simulations.
• Population Stratification: Simulates genetically homogeneous and stratified populations to reflect diverse population structures.
• Preservation of Genetic Structure: Retains allele frequencies and LD structures from the original genome-wide association samples in the simulated datasets.

Scientific Applications:

• Statistical method development and evaluation: Provides realistic genotype data for developing and benchmarking statistical methods for genetic association studies.
• Evaluation of higher-order genetic effects: Facilitates assessment of epistasis and gene-by-environment interaction models using spiked-in multi-SNP effects.
• Validation and benchmarking of association analyses: Enables testing of power, type I error, and robustness of analytical approaches under preserved LD and allele frequency structures.

Methodology:

Resamples triad genotypes from existing genome-wide association case-parent triads and augments them with hypothetical complement triads; offspring traits are assigned probabilistically using user-defined risk models while preserving allele frequencies and LD.