Epigenetic marks of in utero exposure to gestational diabetes and childhood adiposity outcomes: the EPOCH study

• Published in: Diabetic medicine Vol. 35; no. 5; pp. 612 - 620
• Main Authors: Yang, I. V., Zhang, W., Davidson, E. J., Fingerlin, T. E., Kechris, K., Dabelea, D.
• Format: Journal Article
• Language: English
• Published: England Wiley Subscription Services, Inc 01-05-2018
• Subjects: Adaptor Proteins, Vesicular Transport - genetics; Adipose tissue; Adiposity - genetics; Association analysis; Case-Control Studies; Child; Children; Cohort Studies; Cord blood; Diabetes; Diabetes mellitus; Diabetes, Gestational - genetics; DNA methylation; DNA Methylation - genetics; Epigenesis, Genetic; Epigenetics; Epigenomics; Female; Fetal Blood; Gestational diabetes; Humans; Intrauterine exposure; Male; Offspring; Pediatric Obesity - genetics; Peripheral blood; Pregnancy; Prenatal Exposure Delayed Effects - genetics
• ISSN: 0742-3071; 1464-5491
• DOI: 10.1111/dme.13604

Aims
To identify gestational diabetes mellitus exposure‐associated DNA methylation changes and assess whether such changes are also associated with adiposity‐related outcomes.
Methods
We performed an epigenome‐wide association analysis, using Illumina 450k methylation arrays, on whole blood collected, on average, at 10.5 years of age from 81 gestational diabetes‐exposed and 81 unexposed offspring enrolled in the EPOCH (Exploring Perinatal Outcomes in Children) study, and on the cord blood of 31 gestational diabetes‐exposed and 64 unexposed offspring enrolled in the Colorado Healthy Start cohort. Validation was performed by pyrosequencing.
Results
We identified 98 differentially methylated positions associated with gestational diabetes exposure at a false discovery rate of <10% in peripheral blood, with 51 loci remaining significant (plus additional 40 loci) after adjustment for cell proportions. We also identified 2195 differentially methylation regions at a false discovery rate of <5% after adjustment for cell proportions. We prioritized loci for pyrosequencing validation and association analysis with adiposity‐related outcomes based on strengths of association and effect size, network and pathway analysis, analysis of cord blood, and previous publications. Methylation in six out of nine (67%) gestational diabetes‐associated genes was validated and we also showed that methylation of SH3PXD2A was significantly (P<0.05) associated with multiple adiposity‐related outcomes.
Conclusions
Our findings suggest that epigenetic marks may provide an important link between in utero exposure to gestational diabetes and obesity in childhood, and add to the growing body of evidence that DNA methylation is affected by gestational diabetes exposure.
What's new?
We identified DNA methylation changes in childhood that are influenced by in utero exposure to gestational diabetes mellitus (GDM).
Some of the GDM‐associated DNA methylation changes also have an effect on childhood adiposity‐related outcomes.
This study adds to the growing body of evidence that DNA methylation is affected by GDM exposure.
These findings also suggest that epigenetic marks may provide an important link between in utero exposure to GDM and childhood obesity.