Evidence for monozygotic twin (MZ) discordance in methylation level at two CpG sites in the promoter region of the catechol-O-methyltransferase (COMT) gene.
Monozygotic (MZ) twin concordance for a range of psychiatric conditions is rarely 100%. It has been suggested that epigenetic factors, such as DNA methylation, may account for a proportion of the variation in behavioral traits observed between these genetically identical individuals. In this study we have quantitatively assessed the methylation status of two CpG sites in the promoter region of the COMT gene in 12 MZ twins-pairs discordant for birth weight, but otherwise clinically unaffected. DNA was obtained at age 5-years using buccal swabs, and modified using sodium-bisulfite treatment. Methylation profiles were assessed using Pyrosequencing, a technology enabling the precise degree of methylation to be assessed at any CpG site. We found that the degree of methylation at the two CpG sites was highly correlated, but there was considerable variation in the concordance of methylation levels between MZ twin-pairs. Some MZ twin-pairs showed a high degree of methylation concordance, whereas others differed markedly in their methylation profiles. Such epigenetic variation between genetically identical individuals may play a key role in the etiology of psychopathology, and explain the incomplete phenotypic concordance observed in MZ twins.
MRC Social, Genetic and Developmental Psychiatry Research Centre, Institute of Psychiatry, King's College, London, United Kingdom.
Jonathan
J
Mill
Emma
E
Dempster
Avshalom
A
Caspi
Benjamin
B
Williams
Terrie
T
Moffitt
Ian
I
Craig
D001665:Binding Sites / Q000235:genetics; D002394:Catechol O-Methyltransferase / Q000235:genetics*; D002675:Child, Preschool; D018899:CpG Islands / Q000235:genetics*; D004247:DNA / Q000235:genetics / Q000378:metabolism; D019175:DNA Methylation; D005260:Female; D006801:Humans; D008297:Male; D011401:Promoter Regions, Genetic / Q000235:genetics*; D014430:Twins, Monozygotic / Q000235:genetics*
D004247:DNA; D002394:Catechol O-Methyltransferase