If you think the best thing about being an identical twin is pulling off great pranks in school, think again. Identical (monozygotic) twins can also use their powers for good. The lab of Jane Worthington (University of Manchester, UK) has harnessed the power of twins to examine DNA methylation in Rheumatoid Arthritis (RA). Because RA has both genetic and environmental factors contributing to its etiology, twin studies are especially useful. First author Amy Webster noted that “Studying twins allowed us to see DNA methylation changes clearly, as we can be sure they are not confounded by differences in the DNA sequence”.
The talented team looked at 79 pairs of identical twins discordant for RA, where one twin has RA and the other twin does not. They utilized the 450K array to examine whole blood from their discordant twin groups. Importantly, this team looked beyond differentially methylated positions (DMPs); they also looked at differentially variable positions (DVPs). DVPs may only show slight differences in the average degree of methylation at a particular CpG site but have larger differences in the variance and range of values.
Here’s what they found:
- When comparing RA-affected twins to healthy twins they found no significant DMPs, but identified 1171 DVPs
- 763 DVPs in RA twins and 408 DVPs in healthy twins
- 82% of all the DVPs trended towards hypomethylation
- Two highly variable CpG sites are within the binding site for the transcription factor RUNX3
- RUNX3 has been previously associated with RA, and implicated in the development of other immune-related diseases
- Annotation of the RA-associated DVPs revealed several pathways related to the cellular stress response—including the oxidative stress response—which has a known role in RA pathogenesis
RA-associated DVPs were also found to overlap with DVPs identified in type 1 diabetes, which may reveal a larger role for methylation hypervariability in inflammation and immune response. Webster concludes that “In the future, these findings could provide insight into how rheumatoid arthritis could be treated or even better, prevented from developing in the first place”.
To read more about this twin win, head over to Genome Medicine, September 2018.