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The affected sib method. V. Testing the assumptions.

E J Louis1, H Payami, G Thomson

  • 1Department of Genetics, University of California, Berkeley 94720.

Annals of Human Genetics
|January 1, 1987
PubMed
Summary
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Affected sib methods for HLA-associated diseases are robust, even when core assumptions like no recombination or selection are violated. This study details how deviations impact genetic inference, confirming reliability in many scenarios.

Area of Science:

  • Genetics
  • Epidemiology
  • Biostatistics

Background:

  • Affected sib methods are crucial for identifying genetic components of HLA-associated diseases.
  • These methods rely on several assumptions that may not hold true in real-world populations.

Purpose of the Study:

  • To investigate the impact of violated assumptions on affected sib methods.
  • To derive haplotype sharing identity by descent (IBD) expectations under various conditions.

Main Methods:

  • Explicitly derived IBD expectations for selection against affected individuals and recombination.
  • Derived expectations for non-random mating, admixture, meiotic drive, and environmental factors.
  • Described expectation spaces of haplotype sharing for affected sib pairs and trios under a single diallelic locus model.

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Main Results:

  • The effects of violating assumptions on haplotype sharing and disease parameter estimation vary significantly.
  • Each considered factor (selection, recombination, mating, etc.) influences results differently.
  • The study quantifies these impacts for affected sib pairs and trios.

Conclusions:

  • Affected sib methods demonstrate robustness across many scenarios, despite potential assumption violations.
  • Understanding these deviations is key to accurate genetic inference in HLA-associated diseases.
  • The findings support the continued use of affected sib methods with careful consideration of underlying assumptions.