Epigenome-wide association study in blood of children born to a mother with or without type 1 diabetes

Type 1 diabetes (T1D) has a strong genetic background and therefore, familial aggregation of the disease is common. The risk for T1D, however, differs depending on the affected family member. Children born to a mother with T1D have a reduced risk compared to children having a father with T1D. This relative protection offered by a mother remains a longstanding phenomenon with largely unexplored mechanisms. Changes in the epigenome, such as DNA methylation, during early life development in children exposed to maternal T1D may contribute to the protection. We performed a meta-analysis of epigenome-wide association studies (EWASs) in 1,752 young children born to a mother living with or without type 1 diabetes (790 children with a mother with T1D). All children had a higher risk for the development of T1D, defined by either a first-degree family member with T1D or a genetic risk score. We analyzed differential methylation of 651,271 cytosine-phosphate-guanine (CpG) sites and 41,360 methylated regions (DMRs) by robust linear regression by maternal T1D status (adjusted for age at sample, sex, the first three principal components, and six estimated blood cell types). Multiple correction was performed using FDR according to Benjamini-Hochberg. We excluded all CpGs with high heterogeneity (I^2>75) between the studies (35,350 CpGs). The dataset includes the summary statistics of the CpG and DMR meta-EWAS (genomic positions according to hg19). More information can be found in the publication.