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Affected sib-pair tests for linkage: type I errors with dependent sib-pairs

F Meunier¹, A Philippi, M Martinez

¹INSERM U. 358, Hôpital Saint-Louis, Paris, France.

Genetic Epidemiology

|January 1, 1997

Summary

Affected-sib-pair (ASP) tests are robust for multiple affected sibships. A novel weighting procedure for identical by descent (IBD) information improves test efficiency and robustness, even with missing parental data.

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Area of Science:

Genetics
Statistical Genetics
Bioinformatics

Background:

Affected-sib-pair (ASP) analysis is a common method in genetic linkage studies.
Evaluating the robustness of ASP tests in complex family structures is crucial for accurate genetic association studies.

Purpose of the Study:

To compare the robustness of different affected-sib-pair (ASP) test strategies for multiple affected sibships.
To evaluate the impact of weighting procedures and missing parental data on ASP test performance.

Main Methods:

Simulated multiple affected sibships data.
Assessed type I error rates and test efficiency under various weighting schemes.
Investigated the effect of missing parental marker data on test outcomes.

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Main Results:

Forming all possible pairs slightly increased type I errors.
Common weighting procedures reduced test efficiency.
A novel weighting method, accounting for reduced variance of weighted identical by descent (IBD) information, demonstrated robustness.
Missing parental marker data consistently decreased type I errors across all tested methods.

Conclusions:

The proposed weighting procedure offers a robust approach for ASP analysis in multiple affected sibships.
Careful consideration of weighting methods and handling of missing data is essential for reliable genetic association findings.