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Research Article
Sine Knorr
Aarhus University Hospital
Corresponding Author
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This work is licensed under a CC BY 4.0 License. Read Full License
Background: Offspring born to women with pregestational type 1 diabetes (T1DM) are exposed to an intrauterine hyperglycemic milieu and has an increased risk of metabolic disease in later in life. In this present study we hypothesize that in utero exposure to T1DM alters offspring DNA methylation and gene expression, thereby altering their risk of future disease.
Design: Follow-up study using data from the Epigenetic, Genetic and Environmental Effects on Growth, Metabolism and Cognitive Functions in Offspring of Women with Type 1 Diabetes (EPICOM) collected between 2012-2013.
Setting: Exploratory sub study using data from the nationwide EPICOM study.
Participants: Adolescent offspring born to women with T1DM (n=20) and controls (n=20) matched on age, sex and postal code.
Main outcome measures: This study investigates DNA methylation using the 450K-Illumina Infinium assay® and RNA expression (RNA sequencing) of leucocytes from peripheral blood samples.
Results: We identified 9 hypermethylated and 5 hypomethylated positions (p < 0.005, |DM-value| > 1). RNA expression profiling identified 38 up- and 1 down-regulated genes (p < 0.005, log2FC ≥ 0.3.). Functional enrichment analysis revealed enrichment in ontologies related to diabetes, carbohydrate and glucose metabolism, pathways including MAPK1/MAPK3 and MAPK family signaling and genes related to T1DM, obesity and atherosclerosis. Lastly, by integrating the DNA methylation and RNA expression data, we identified six genes where relevant methylation changes corresponded with RNA expression (CIITA, TPM1, PXN, ST8SIA1, LIPA, DAXX).
Conclusions: Findings suggest the possibility for intrauterine hyperglycemia to impact later life methylation and gene expression, a profile that may be linked to the increased risk of metabolic disease.
Keywords
Type 1 Diabetes, Pregnancy, Epigenetics, Methylation, Transcriptome
Figure 1
Figure 2
Figure 3
Figure 4
Competing interest reported. CHG has given talks for Novo Nordisk (NN). PD is participating in multicenter and multinational clinical studies on the use of insulin in pregnant women with pre-existing diabetes in collaboration with NN; no personal honorarium is involved. None of the study funders had any role in study design, collection, analysis, interpretation, preparation of the manuscript or in the decision to submit the article for publication.
This is a list of supplementary files associated with this preprint. Click to download.
- OnlineSupplementalMaterialFIGURES1.pdf
- OnlineSupplementalMaterialFIGURES2.pdf
- OnlineSupplementalMaterialslegends.docx
- OnlineSupplementalMaterialTABLES1.xlsx
- OnlineSupplementalMaterialTABLES2.xlsx
- OnlineSupplementalMaterialTABLES3.xlsx
- OnlineSupplementalMaterialTABLES4.xlsx
- OnlineSupplementalMaterialTABLES5.xlsx
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This preprint is under consideration at Scientific Reports. A preprint is a preliminary version of a manuscript that has not completed peer review at a journal. Research Square does not conduct peer review prior to posting preprints. The posting of a preprint on this server should not be interpreted as an endorsement of its validity or suitability for dissemination as established information or for guiding clinical practice.
Learn more about In Review
Research Article
Sine Knorr
Aarhus University Hospital
Corresponding Author
Badges
Prescreen
This manuscript passed our Prescreen assessment
Complete author information
Appropriate declaration statements
Potential risks to human health
Prescreen
Peer Review Timeline
CURRENT STATUS: Under Review
Version 1
Posted 18 Nov, 2021
No community comments so far
Editor assigned
On 30 Nov, 2021
Editor invited
On 15 Nov, 2021
Submission checks complete
On 15 Nov, 2021
First submitted
On 03 Nov, 2021
Metrics
Comments: 0
PDF Downloads: ...
HTML Views: ...
License:
This work is licensed under a CC BY 4.0 License. Read Full License
Background: Offspring born to women with pregestational type 1 diabetes (T1DM) are exposed to an intrauterine hyperglycemic milieu and has an increased risk of metabolic disease in later in life. In this present study we hypothesize that in utero exposure to T1DM alters offspring DNA methylation and gene expression, thereby altering their risk of future disease.
Design: Follow-up study using data from the Epigenetic, Genetic and Environmental Effects on Growth, Metabolism and Cognitive Functions in Offspring of Women with Type 1 Diabetes (EPICOM) collected between 2012-2013.
Setting: Exploratory sub study using data from the nationwide EPICOM study.
Participants: Adolescent offspring born to women with T1DM (n=20) and controls (n=20) matched on age, sex and postal code.
Main outcome measures: This study investigates DNA methylation using the 450K-Illumina Infinium assay® and RNA expression (RNA sequencing) of leucocytes from peripheral blood samples.
Results: We identified 9 hypermethylated and 5 hypomethylated positions (p < 0.005, |DM-value| > 1). RNA expression profiling identified 38 up- and 1 down-regulated genes (p < 0.005, log2FC ≥ 0.3.). Functional enrichment analysis revealed enrichment in ontologies related to diabetes, carbohydrate and glucose metabolism, pathways including MAPK1/MAPK3 and MAPK family signaling and genes related to T1DM, obesity and atherosclerosis. Lastly, by integrating the DNA methylation and RNA expression data, we identified six genes where relevant methylation changes corresponded with RNA expression (CIITA, TPM1, PXN, ST8SIA1, LIPA, DAXX).
Conclusions: Findings suggest the possibility for intrauterine hyperglycemia to impact later life methylation and gene expression, a profile that may be linked to the increased risk of metabolic disease.
Figure 1
Figure 2
Figure 3
Figure 4
Competing interest reported. CHG has given talks for Novo Nordisk (NN). PD is participating in multicenter and multinational clinical studies on the use of insulin in pregnant women with pre-existing diabetes in collaboration with NN; no personal honorarium is involved. None of the study funders had any role in study design, collection, analysis, interpretation, preparation of the manuscript or in the decision to submit the article for publication.
This is a list of supplementary files associated with this preprint. Click to download.
- OnlineSupplementalMaterialFIGURES1.pdf
- OnlineSupplementalMaterialFIGURES2.pdf
- OnlineSupplementalMaterialslegends.docx
- OnlineSupplementalMaterialTABLES1.xlsx
- OnlineSupplementalMaterialTABLES2.xlsx
- OnlineSupplementalMaterialTABLES3.xlsx
- OnlineSupplementalMaterialTABLES4.xlsx
- OnlineSupplementalMaterialTABLES5.xlsx
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