Affected sibpair linkage tests for multiple linked susceptibility genes

Genet Epidemiol. 1997;14(2):103-15. doi: 10.1002/(SICI)1098-2272(1997)14:2<103::AID-GEPI1>3.0.CO;2-8.

Abstract

Genome-wide searches for susceptibility genes using pairs of affected siblings are being undertaken to dissect out individual polygenes that contribute to human multifactorial disease. Efficient identity-by-descent (IBD)-based sibpair linkage tests are available that test individual markers or maps of linked markers for linkage to a single putative susceptibility gene. In order to assess the support for linkage to a second putative susceptibility gene that happens to map close to an established susceptibility gene, it is necessary to use a method that correctly allows for the IBD distortion that directly results from the linkage between the two genes. A maximum likelihood-based, multilocus linkage test is proposed, which accounts for this interdependency and evaluates the support for an interaction between constituent susceptibility genes. The size and power of a test for a second linked susceptibility gene is investigated by simulation studies.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Chromosome Mapping
  • Computer Simulation
  • Genetic Linkage*
  • Genetic Predisposition to Disease
  • Humans
  • Lod Score
  • Meiosis / genetics*
  • Models, Statistical
  • Pedigree