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Related Experiment Videos

Genetic association tests with age at onset.

L Hsu1

  • 1Division of Public Health Sciences, Biostatistics Modeling and Methods, Fred Hutchinson Cancer Research Center, MP-665, PO Box 19024, Seattle, WA 98109-1024, USA. lih@fhcrc.org

Genetic Epidemiology
|January 28, 2003
PubMed
Summary

Incorporating age at onset into genetic association tests like the transmission disequilibrium test (TDT) can increase power, especially for common diseases. Old unaffected individuals can significantly boost TDT power for genetic marker analysis.

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Area of Science:

  • Genetics
  • Biostatistics
  • Epidemiology

Background:

  • Diseases and traits often present with a variable age at onset.
  • Traditional genetic association tests may not fully leverage age-at-onset information.
  • Previous studies suggest limited impact of age-at-onset data on transmission disequilibrium tests (TDT).

Purpose of the Study:

  • To evaluate the statistical power of the TDT based on age at onset.
  • To determine conditions under which age-at-onset information enhances TDT power.
  • To propose and assess a modified test statistic for marker-age at onset association.

Main Methods:

  • Evaluation of TDT power as a function of age at onset.
  • Simulation studies using trio and sibling-cluster sampling schemes.

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  • Comparison of a proposed modified test statistic against the standard TDT.

    • Main Results:

    • Age-at-onset information is most beneficial for common diseases or when genotype relative risk varies with age.
    • Extremely old unaffected subjects can substantially increase TDT power, comparable to old-onset cases.
    • The proposed modified test statistic shows promise in detecting associations between genetic markers and age at onset.

    Conclusions:

    • Age-at-onset data can significantly improve the power of genetic association studies, particularly the TDT.
    • The utility of age-at-onset information is context-dependent, influenced by disease prevalence and age-specific risks.
    • A modified TDT approach offers a valuable tool for analyzing genetic associations with age at onset.