Gene-disease Association Studies

An alternative approach to identifying disease susceptibility gene variants is based on the concept of association. Whilst linkage deals with a specific genetic relationship between loci on a chromosome, association describes a statistical relationship between genes or genetic variants and the disease of interest.

The aim of association studies is to identify disease susceptibility gene variants by comparing genetic variants between people with and without the disease of interest.

As with any association study, the results generated need to be interpreted very carefully, as any particular association between a genetic variant and a disease does not mean that the variant is important in causation.

There are four possible explanations for the finding of a positive association:

  1. One possibility is that the association has been found by chance. In other words there is a statistical link, but not a link at the level of disease causation.
  2. Alternatively, it may be that an apparent association is the result of the limitations of the study method. An example that could suggest a false association is linkage disequilibrium. This is seen when the genetic variant measured in the study is not the true disease-causing variant but is situated close to it on the same stretch of DNA. -
  3. Different genetic variants are known to occur with varying frequencies in different populations and ethnic groups, quite independent of the frequency of disease in these groups. As a result cases and controls may be selected from genetically different subsets of a population, where the frequency of the disease and genetic variant are especially common in one of these subsets. This results in the assumption that there is a link between a particular genetic variant and the disease of interest. This type of bias (which may be called confounding) is termed population stratification.
  4. The genetic variant is important in disease causation.

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