COMT

rs4680

COMT breaks down messengers such as dopamine and noradrenaline. The Val158Met variant (rs4680) changes enzyme activity and thereby the dopamine level in the prefrontal cortex. Effects on cognition, stress processing and pain are described, but small and context-dependent.

Val158Met

The variant swaps valine for methionine at position 158. The Met enzyme is about three to four times less active and thus more thermolabile. Because COMT handles a large share of dopamine breakdown in the prefrontal cortex, the variant shifts the dopamine tone there.

The trade-off model

More prefrontal dopamine (Met) can favour working memory under calm conditions but be disadvantageous under stress; the reverse holds for Val. Hence the terms worrier and warrior. These are tendencies with small effect sizes, not fixed types.

Context

rs4680 is a popular but over-interpreted example. Individual studies contradict each other, and replications are often weaker than the first reports. Genome shows the genotype as information, not as a personality test.

What Genome measures. The genotype at rs4680 (Val158Met) and the resulting tendency of enzyme activity (Val fast, Met slow).

Related topics

rsIDs, microarray and SNP lookupPharmacogenetics

Sources

  1. 1Egan et al., 2001 Effect of COMT Val108/158 Met genotype on frontal lobe function and risk for schizophrenia. PNAS 98:6917–6922. doi.org/10.1073/pnas.111134598
  2. 2Tunbridge et al., 2006 Catechol-O-methyltransferase, cognition, and psychosis: Val158Met and beyond. Biological Psychiatry 60:141–151. doi.org/10.1016/j.biopsych.2005.10.024