Affected Sibpair Linkage Tests for Multiple Linked Susceptibility Genes
Martin Farrall
Genetic Epidemiology ,
14(2), 103-115 (1997)
Abstract
Genome-wide searches for susceptibility genes using pairs of
affected siblings are being undertaken to dissect out individual
polygenes that contribute to human multi-factorial diseases.
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 potative 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.