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Sequential haplotype scan methods for association analysis.

Zhaoxia Yu1, Daniel J Schaid

  • 1Division of Biostatistics, Department of Health Sciences Research, Mayo Clinic College of Medicine, Rochester, Minnesota 55905, USA.

Genetic Epidemiology
|May 10, 2007
PubMed
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This study introduces a sequential haplotype scan method for efficiently identifying genetic markers associated with disease. The approach enhances power in genetic association studies while improving computational efficiency compared to existing methods.

Area of Science:

  • Genetics
  • Statistical genetics
  • Computational biology

Background:

  • Multi-locus and haplotype-based analyses offer greater power for detecting disease susceptibility loci than single-locus analyses.
  • However, irrelevant markers can increase computational complexity and reduce the effectiveness of these analyses.
  • Exhaustive searches for optimal marker combinations are computationally intensive.

Purpose of the Study:

  • To develop a computationally efficient sequential haplotype scan method for identifying combinations of adjacent markers associated with disease status.
  • To evaluate the performance of this new method against single-locus and sliding window approaches.

Main Methods:

  • A sequential approach was developed, adding adjacent markers based on their conditional contribution to haplotype association with disease, utilizing the Mantel-Haenszel statistic.

Related Experiment Videos

  • Two permutation-based methods were proposed for evaluating growing haplotypes: a combined marker method and a conditional statistic summation method.
  • The methods were validated using simulated data and applied to experimental CYP2D6 data.

    • Main Results:

    • The sequential haplotype scan successfully identified sets of adjacent markers with potential strong genetic effects or linkage disequilibrium with disease predisposing variants.
    • The proposed methods demonstrated greater power in detecting associations compared to the single-locus method.
    • The sequential scan was significantly more computationally efficient than sliding window methods.

    Conclusions:

    • The sequential haplotype scan method is an effective and computationally efficient tool for identifying disease-associated marker haplotypes.
    • This approach can improve the power of genetic association studies by efficiently handling multi-locus data.
    • The method holds promise for discovering complex genetic architectures underlying diseases.