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A permutation test for the robust sib-pair linkage method

Y Wan1, J Cohen, R Guerra

  • 1Department of Statistical Science, Southern Methodist University, Dallas, Texas 75275, USA.

Annals of Human Genetics
|January 1, 1997
PubMed
Summary
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A new permutation test for linkage analysis offers a genetically motivated alternative to the traditional t-test. This robust sib-pair method provides a natural approach for evaluating genetic linkage, even with complex family structures.

Area of Science:

  • Genetics
  • Statistical genetics
  • Bioinformatics

Background:

  • The Haseman & Elston (1972) sib-pair method is a widely used allele-sharing approach for genetic linkage analysis.
  • Traditional linkage analysis often employs a standard t-test, despite potential violations of underlying statistical assumptions.
  • Concerns exist regarding the validity of the t-test in certain linkage analysis scenarios.

Purpose of the Study:

  • To introduce a permutation-based reference distribution for the Haseman & Elston regression coefficient estimate.
  • To provide a genetically principled alternative to standard regression testing procedures in linkage analysis.
  • To evaluate the performance of the permutation test and compare it with the conventional t-test.

Main Methods:

  • Developed a permutation test leveraging genetic principles to approximate Mendelian co-segregation under the null hypothesis of no linkage.

Related Experiment Videos

  • Applied the permutation test to real genetic data, specifically analyzing two well-characterized lipoprotein systems.
  • Conducted theoretical analysis and simulations to assess the accuracy and robustness of the permutation test.

    • Main Results:

    • The permutation test provides a natural approach for linkage analysis by approximating Mendelian co-segregation.
    • Theoretical analysis and simulations demonstrate that the conventional t-test closely approximates the permutation test results.
    • The approximation holds even when analyzing dependent sib pairs, indirectly validating the t-test's application.

    Conclusions:

    • The permutation test offers a robust and genetically grounded method for linkage analysis.
    • The conventional t-test is a reasonable approximation of the permutation test, even with dependent sib pairs.
    • The developed permutation test is applicable to real-world genetic data, as demonstrated with lipoprotein systems.