Advances and Applications in Statistics
Volume 1, Issue 3, Pages 277 - 308
(December 2001)
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TRANSMISSION DISEQUILIBRIUM TEST OF TWO UNLINKED DISEASE LOCI; APPLICATION TO RESPIRATORY DISTRESS SYNDROME
Ruzong Fan (U. S. A.), Joanna Floros (U. S. A.) and Momiao Xiong (U. S. A.)
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Abstract: The transmission disequilibrium test (TDT) for one
disease locus is a powerful method for detection of
linkage in the presence of association between a
marker locus and a disease locus and has been studied
extensively in recent years. However, the majority of
common diseases involves multiple disease loci. In
this paper, we extend the TDT for one disease locus to
two unlinked disease loci. We consider a two-marker-
locus and two-disease-locus model. Each of the two
disease loci is hypothesized to be linked to one of
the two marker loci. Moreover, the two disease loci
are assumed to be unlinked. Based on transmission
probabilities of the alleles at the two marker loci,
we propose test statistics to test linkage in the
presence of association between two disease loci and
two marker loci. We present an analytic method for
calculating the power of the two-locus TDT. We compare
the power and sample size of the TDT of one-locus
models with that of the two-locus TDT for six types of
genetic inheritance patterns. The power to detect
linkage with TDT for two unlinked disease locus model
is higher than that of the traditional TDT for one
disease locus model if the disease is controlled by
two loci. Hence, the TDT of two unlinked disease loci
model is more powerful than the one disease locus TDT
in the presence of two disease loci for mapping
disease genes. In cases, where it is known that one
disease locus is linked to a marker, we propose
conditional TDT statistics to test if a second disease
locus is linked to another marker locus with which it
interacts to influence the disease trait with the
known disease locus. The conditional TDT statistics
are potentially useful in genomewide screening.
Finally, the proposed two-marker-locus and
two-disease-locus TDT is illustrated with data from
genetic studies of Respiratory Distress Syndrome
(RDS). |
Keywords and phrases: allele transmission probabilities, genomewide screening, linkage disequilibrium, TDT statistics, power and sample size, respiratory distress syndrome. |
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