POLY

POLY performs polygenic analysis and analytical power assessment for variance component linkage studies of human quantitative traits in large pedigrees.

Key Features:

• Variance component linkage analysis: Maps quantitative trait loci (QTLs) using variance component linkage analysis optimized for large pedigrees.
• Analytical power computation: Approximates the noncentrality parameter of the likelihood-ratio test via Taylor expansions to provide rapid analytical power estimates.
• Efficient IBD moment computations: Computes the second and third moments of the identical by descent (IBD) sharing distribution while exploiting natural pedigree symmetries.
• Simulation validation: Validated accuracy of power calculations using simulations of pedigrees with 2–5 generations and 2–8 siblings per sibship.
• Application to large cohorts: Applied analytical power calculations to a cohort of 6,148 Sardinians including a pedigree of 625 phenotyped individuals across 98 quantitative traits.
• Comparison with SNP mapping panels: Demonstrated via simulations on eight representative traits that power estimates assuming fully informative markers closely align with those from a SNP mapping panel (>1 SNP/cM).

Scientific Applications:

• QTL mapping in large pedigrees: Identification and localization of quantitative trait loci in extensive family structures.
• Study design and power assessment: Analytical estimation of linkage study power for planning sample sizes and pedigree ascertainment in human quantitative-trait studies.
• Evaluation of marker informativeness: Comparative assessment of power under fully informative markers versus SNP mapping panels (>1 SNP/cM).

Methodology:

Approximates the noncentrality parameter of the likelihood-ratio test using Taylor expansions; computes second and third moments of the IBD sharing distribution exploiting pedigree symmetries; validates calculations via pedigree simulations (2–5 generations, 2–8 siblings per sibship).