DNA methylation at CpG dinucleotides is associated with gene silencing, stress, and memory. The catechol-O-methyltransferase (COMT) Val(158) allele in rs4680 is associated with differential enzyme activity, stress responsivity, and prefrontal activity during working memory, and it creates a CpG dinucleotide. The authors report that methylation of the Val(158) allele of Val/Val humans was associated negatively with lifetime stress and positively with working memory performance. They suggest that stress-related methylation is associated with silencing of the gene, which partially compensates the physiological role of the high-activity Val allele in prefrontal cognition and activity. Stress-related DNA methylation is an example of how genes and the environment may interact to affect brain function.

Ursini G et al. Stress-Related Methylation of the Catechol-O-Methyltransferase Val158 Allele Predicts Human Prefrontal Cognition and Activity. J. Neuroscience 31(18):6692-6698 (2011)    http://www.ncbi.nlm.nih.gov/pubmed/21543598