Extension to Sib-pair Linkage Tests Applicable
to Disorders Characterized by Delayed Onset
D.V. Dawson, E.B. Kaplan, R.C. Elston
Genetic Epidemiology,7, 453-466 (1990)
Abstract
Extensions of the approach to sib-pair linkage tests developed by
Haseman and Elston [Behav Genet 2:3-19, 1972] are proposed which
incorporate information on age of onset and age at examination.
Alternate sources for the age of onset corrections are described,
including models for the estimation of parameters associated with
the age of onset distribution. Simulation is used to examine the
performance of the approach when applied to a dominant disorder of
late onset for a range of recombination fractions ranging from very
tight linkage to free recombination. For each set of genetic
parameters, 2,000 samples of 50 four-member sibships were generated
under a complete ascertainment model to investigate power and Type I
error, and to compare variants of the proposed technique. Results
with and without age-of-onset correction are compared to each other
and to those obtainable if penetrance were complete, i.e., if there
were no intervening age-of-onset phenomenon. Results from simulation
studies show that significance probabilities are enhanced in the
presence of linkage when age-of-onset extensions are used. The
proposed methods are associated with acceptable levels of Type I
error, and substantive gains in power are obtained when data related
to age of onset and age at examination are incorporated into the
analysis.
Allele-sharing linkage analysis