Monozygotic (MZ), or identical, twins may seem like exact carbon copies of each other, but recent work has shown that epigenetic variation between them is common, even though they share an identical genome. Sometimes these small but significant epigenetic differences are suspected to lead to very different outcomes when it comes to psychiatric disorders like schizophrenia (SZ) and bipolar disorder (BD), which is what researchers from King’s College London explored in a new Human Molecuar Genetics paper.
“In this study we aimed to see whether epigenetic differences between MZ twins were associated with discordance for a diagnosis of either schizophrenia or bipolar disorder.” Explained corresponding author Jonathan Mill. The UK group studied DNA methylation in twins using bead-based arrays with those results validated by EpiTYPTER assays to uncover solid data for further analysis.
According to Mill, “It was striking that many of the regions we found to be differentially methylated in the affected twins were near genes with functional relevance to psychosis.” A few more important takeaways from this project were:
- There were quite a few disease-relevant methylation differences between MZ twins discordant for psychosis. Some of these were observed in all discordant twin-pairs, while others seemed to be linked to families, and may reflect the heterogeneity inherent in these disorders.
- The top psychosis-associated DMR found in the twin blood samples, was also hypomethylated in some post-mortem brain samples from affected individuals. “This could indicate that blood samples may be useful for detecting disease-associated epigenetic changes in less accessible tissues such as the brain.” Says Mill.
- Pathway analysis of the differentially methylated loci between discordant twins showed a connection to functional networks associated with neuropsychiatric disease.
So, now that there’s evidence that ties aberrant DNA methylation to psychosis, the question is: What’s causing those DNA methylation changes?
“This is one thing we could not address in this study. In fact, it is difficult given the cross-sectional design of the study to conclude whether the changes are actually a cause or result of psychosis. We know, for instance, that many medications used in the treatment of psychosis have effects on the epigenetic regulation of gene expression.” Explains Mill. Your classic chicken-or-the-egg situation…at least until the next round of experiments is done.
Take a double-dose of all the data at Human Molecular Genetics, September 2011.