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Related Experiment Videos

Assessing the effect of multiple linkage tests in complex diseases.

F Clerget-Darpoux1, M C Babron, C Bonaïti-Pellié

  • 1INSERM U155, Paris, France.

Genetic Epidemiology
|January 1, 1990
PubMed
Summary

Assessing a lod score of 3 in genetic linkage studies is challenging due to multiple tests. We demonstrate that a lod score of 3 may occur by chance, even without true linkage between a genetic marker and complex disease.

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Area of Science:

  • Genetics
  • Biostatistics

Background:

  • Linkage studies aim to identify genetic markers associated with diseases.
  • A lod score of 3 is traditionally considered suggestive of linkage.
  • Assessing significance is complicated by the potential for multiple, independent testing.

Purpose of the Study:

  • To evaluate the statistical significance of a lod score of 3 in complex disease linkage studies.
  • To investigate the impact of multiple testing on lod score interpretation.

Main Methods:

  • Statistical analysis of linkage data under various genetic models.
  • Simulation of independent transmission of disease and marker.
  • Calculation of the probability of achieving a lod score of 3 by chance.

Main Results:

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  • The probability of obtaining a lod score of 3 under independent transmission is non-negligible.
  • Multiple testing increases the likelihood of observing a lod score of 3 without true linkage.

Conclusions:

  • A lod score of 3 should be interpreted cautiously in the context of complex disease linkage studies.
  • The possibility of false positives due to chance and multiple testing must be considered.