Identification of Type 1 Diabetes–Associated DNA Methylation Variable Positions That Precede Disease Diagnosis
2011

Identifying DNA Methylation Changes Linked to Type 1 Diabetes

Sample size: 15 publication 10 minutes Evidence: moderate

Author Information

Author(s): Rakyan Vardhman K., Beyan Huriya, Down Thomas A., Hawa Mohammed I., Maslau Siarhei, Aden Deeqo, Daunay Antoine, Busato Florence, Mein Charles A., Manfras Burkhard, Dias Kerith-Rae M., Bell Christopher G., Tost Jörg, Boehm Bernhard O., Beck Stephan, Leslie R. David

Primary Institution: Barts and The London School of Medicine and Dentistry, Queen Mary University of London

Hypothesis

Epigenetic variation contributes to the non-genetic component of Type 1 Diabetes (T1D) aetiology.

Conclusion

The study found that specific DNA methylation changes associated with T1D occur early in the disease process, even before diagnosis.

Supporting Evidence

  • 132 different CpG sites were identified that correlated with the diabetic state.
  • T1D–MVPs were confirmed to display significant intra-MZ pair DNA methylation differences.
  • T1D–MVPs were found in individuals before T1D diagnosis.
  • 71% of T1D–MVPs showed expected directionality in pre-T1D samples compared to controls.
  • T1D–MVPs were enriched in singletons positive for diabetes-associated autoantibodies but disease-free.

Takeaway

Scientists looked at DNA changes in twins to find clues about why some people get Type 1 Diabetes and others don't, discovering that these changes happen before the disease shows up.

Methodology

An epigenome-wide association study (EWAS) was performed using DNA methylation profiles from purified CD14+ monocytes of T1D-discordant monozygotic twin pairs.

Potential Biases

Potential biases may arise from the selection of twin pairs and the specific methodologies used for DNA methylation analysis.

Limitations

The study's findings are based on a limited number of twin pairs and may not be generalizable to all populations.

Participant Demographics

Participants were monozygotic twins of European origin, with one twin diagnosed with T1D and the other healthy.

Statistical Information

P-Value

0.035

Statistical Significance

p<0.05

Digital Object Identifier (DOI)

10.1371/journal.pgen.1002300

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