Concordance (genetics)

For other uses, see Concordance.

Concordance as used in genetics usually means the presence of the same trait in both members of a pair of twins. However, the strict definition is the probability that a pair of individuals will both have a certain characteristic, given that one of the pair has the characteristic. For example, twins are concordant when both have or both lack a given trait.[1] Ideally, concordance includes that of identical twins.

Twin studies

A twin study compares the concordance rate of identical twins to that of fraternal twins. This can help determine whether the disease has a genetic cause. Controversial uses of twin data have looked at concordance rates for homosexuality and intelligence.

Because identical twins are genetically identical, it follows that any genetic mutation carried by one would also be carried by the other. If a characteristic identified in one twin is caused by a genetic mutation, then it should also be present in the other twin. Thus, the concordance rate of a given characteristic helps establish whether or to what extent it is caused by genetic mutation.

There are several problems with this assumption:

  1. A given genetic mutation may not have 100% penetrance, in which case it may have different phenotypic consequences in genetically identical individuals;
  2. Developmental and environmental conditions may be different for genetically identical individuals. If developmental and environmental conditions contribute to the development of the disease or other characteristic (as is almost always the case), there can be differences in the outcome of genetically identical individuals;
  3. The logic is further complicated if the characteristic is polygenic, i.e. caused by mutations in more than one gene.
  4. epigenetic effects can alter the genetic expressions in twins through varied exposure of chemicals, dietary habits and environmental factors. The epigenetic effect is least when young and increases with age, as the identical twins grow older.[1]
  5. Where in the absence of one or more environmental factors a condition will not develop in an individual, even with high concordance rates, the proximate cause is environmental, with strong genetic influence: thus "a substantial role of genetic factors does not preclude the possibility that the development of the disease can be modified by environmental intervention." [2] so "genetic factors are assumed to contribute to the development of that disease." but cannot be assumed alone to be causal [3]

Genotyping studies

In genotyping studies where DNA is directly assayed for positions of variance (see SNP), concordance is a measure of the percentage of SNPs that are measured as identical. Samples from the same individual or identical twins theoretically have a concordance of 100%, but due to assaying errors and somatic mutations, they are usually found in the range of 99% to 99.95%. Concordance can therefore be used as a method of assessing the accuracy of a genotyping assay platform.

Because a child inherits half of its DNA from each parent, parents and children, siblings, and fraternal (dizygotic) twins have a concordance around 50% using this measure.

References

  1. ^ R. Lewontin, Human Diversity. (Scientific American Press, 1982)