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Umbilical cord blood DNA methylation in children who later develop type 1 diabetes
Essi Laajala1,2,3,4, Ubaid Ullah Kalim1,2, Toni Grönroos1,2
1Turku Bioscience Centre, University of Turku and Åbo Akademi University, Turku, Finland.
Insights
Perinatal DNA methylation patterns in umbilical cord blood do not appear to predict type 1 diabetes development in children. Further studies with larger datasets may be needed to confirm these findings on early-onset type 1 diabetes.
Area of Science:
- Epigenetics
- Immunology
- Pediatrics
Background:
- Distinct DNA methylation patterns have been observed in whole blood preceding type 1 diabetes in children.
- Investigating perinatal epigenetics may offer insights into early type 1 diabetes prediction.
Purpose of the Study:
- To determine if perinatal DNA methylation in umbilical cord blood is associated with the later progression to type 1 diabetes.
Main Methods:
- Reduced representation bisulphite sequencing (RRBS) was performed on umbilical cord blood samples.
- Cases (n=43) diagnosed with type 1 diabetes and/or multiple islet autoantibodies were compared to autoantibody-negative controls (n=79).
- Pregnancy and maternal confounding factors were analyzed.
Main Results:
- No significant differences in umbilical cord blood methylation patterns were found between type 1 diabetes cases and controls (FDR <0.05).
Conclusions:
- Perinatal DNA methylation does not appear to distinguish children who will develop type 1 diabetes from healthy children.
- Larger sample sizes might be required to detect subtle epigenetic differences.
- Epigenetic changes may occur later in childhood rather than perinatally.
Aims/Hypothesis:
Distinct DNA methylation patterns have recently been observed to precede type 1 diabetes in whole blood collected from young children. Our aim was to determine whether perinatal DNA methylation is associated with later progression to type 1 diabetes.
Methods:
Reduced representation bisulphite sequencing (RRBS) analysis was performed on umbilical cord blood samples collected within the Finnish Type 1 Diabetes Prediction and Prevention (DIPP) Study. Children later diagnosed with type 1 diabetes and/or who tested positive for multiple islet autoantibodies (n = 43) were compared with control individuals (n = 79) who remained autoantibody-negative throughout the DIPP follow-up until 15 years of age. Potential confounding factors related to the pregnancy and the mother were included in the analysis.
Results:
No differences in the umbilical cord blood methylation patterns were observed between the cases and controls at a false discovery rate <0.05.
Conclusions/Interpretation:
Based on our results, differences between children who progress to type 1 diabetes and those who remain healthy throughout childhood are not yet present in the perinatal DNA methylome. However, we cannot exclude the possibility that such differences would be found in a larger dataset.
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