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Related Experiment Videos

Ascertainment issues in variance components models.

M de Andrade1, C I Amos

  • 1Department of Health Sciences Research, Mayo Clinic and Mayo Foundation, Rochester, Minnesota 55905, USA. mandrade@mayo.edu

Genetic Epidemiology
|December 7, 2000
PubMed
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Ascertainment correction methods in family studies of complex diseases have minimal differences. Variance components models are more powerful for rare alleles, while extreme discordant sib pairs designs are better for common alleles.

Area of Science:

  • Biostatistics
  • Genetic Epidemiology
  • Complex Disease Genetics

Background:

  • Ascertainment bias is a major concern in family studies of complex diseases.
  • Existing methods by Elston and Sobel (1979) and Hopper and Mathews (1982) address ascertainment correction for quantitative traits.

Purpose of the Study:

  • To compare the performance of two ascertainment correction methods using a variance components approach.
  • To evaluate the impact of ascertainment on genetic and environmental variance components.
  • To compare a variance components model with ascertainment correction against the extreme discordant sib pairs (EDSP) design.

Main Methods:

  • Simulation studies were conducted for single ascertainment using a variance components approach.
  • Comparison of estimates from two different ascertainment correction methods.

Related Experiment Videos

  • Analysis of ascertained families with and without correction for ascertainment.
  • Comparison of a variance components model with ascertainment correction to the EDSP design for discordant sib pairs.

    • Main Results:

    • Minimal differences were observed between the two methods of ascertainment correction.
    • Ascertainment affected polygenic and environmental variance components but had little impact on the major gene component.
    • The EDSP design showed slightly more power for common alleles.
    • The variance components procedure demonstrated significantly more power for rare alleles.

    Conclusions:

    • Both ascertainment correction methods are comparable in their effectiveness.
    • Ascertainment has a limited impact on major gene detection in complex disease studies.
    • The choice of method (variance components vs. EDSP) depends on the allele frequency of interest.