Causes of association - 2: Linkage disequilibrium

If the pathogenic mutation lies very close to the marker polymorphism then the ancestral marker allele which occurred in a founder bearing the mutation may remain associated with the disease.

The disease mutation was originally introduced to the population by a founder having the D marker allele on the same chromosome as the mutation

Recombination between the mutation and marker will eventually dissipate this association (as can further mutational events). The association will tend to be preserved if there is very tight linkage between the two loci, so it can be described as being due to linkage disequilibrium.

Different alleles of the marker may be associated with the disease in different populations, depending on what founder effects were present. This would not be the case if the marker polymorphism affected risk directly.