Linkage and association studies in complex diseases are used to identify and fine map disease loci.
The process of identifying the aetiological polymorphism, the molecular variant responsible for the
linkage and association of the chromosome region with disease, is complicated by the low penetrance
of the disease variant, the linkage disequilibrium between physically-linked polymorphic markers
flanking the disease variant, and the possibility that more than one polymorphism in the most
associated region is aetiological. It is important to be able to detect additional disease determinants
in a region containing a cluster of genes, such as the major histocompatibility complex (MHC) region
on chromosome 6p21. Some methods have been developed for detection of additional variants, such
as the Haplotype Method, Marker Association Segregation Chi-squares (MASC) Method, and the
Homozygous Parent Test. Here, the Extended Transmission/Disequilibrium Test is adapted to test
for association conditional on a previously associated locus. This test is referred to as the Conditional
Extended TDT (CETDT). We discuss the advantages of the CETDT compared to existing methods
and, using simulated data, investigate the effect of polymorphism, inheritance, and linkage
disequilibrium on the CETDT.