Power and sample size for testing associations of haplotypes with complex traits

Area of Science:

• Genetics
• Statistical Genetics
• Bioinformatics

Background:

• Haplotype association studies are powerful for analyzing quantitative traits and disease status.
• Increasing discovery of single nucleotide polymorphisms (SNPs) drives interest in haplotype analyses.
• Limited guidance exists for sample size determination in haplotype studies, especially with unknown phase or tag-SNPs.

Purpose of the Study:

• To derive analytic methods for determining sample size and power in haplotype association studies.
• To evaluate the impact of unknown haplotype phase on study power.
• To assess the effect of using a subset of tag-SNPs on statistical power.

Main Methods:

• Developed analytic methods for sample size and power calculations based on haplotype frequency distributions.
• Covered both phase-known and phase-unknown haplotype scenarios.
• Extended methods to incorporate tag-SNP selection and evaluate their impact on power.

Main Results:

• Provided accurate theoretical power predictions for haplotype association studies.
• Demonstrated the loss of efficiency associated with unknown haplotype phase.
• Showcased the influence of tag-SNP selection on study power through simulations.

Conclusions:

• The derived analytic formulae offer essential guidance for planning haplotype association studies.
• These methods account for unknown phase and tag-SNP usage, enhancing study design.
• Accurate power predictions support robust genetic association research.