1. Identification of loci where DNA methylation potentially mediates genetic risk of type 1 diabetes.
- Author
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Ye, Jody, Richardson, Tom G., McArdle, Wendy L., Relton, Caroline L., Gillespie, Kathleen M., Suderman, Matthew, and Hemani, Gibran
- Subjects
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DNA methylation , *DISEASE susceptibility , *TYPE 1 diabetes , *BIOMARKERS , *GUANINE , *GENETICS , *DIABETES risk factors - Abstract
The risk of Type 1 Diabetes (T1D) comprises both genetic and environmental components. We investigated whether genetic susceptibility to T1D could be mediated by changes in DNA methylation, an epigenetic mechanism that potentially plays a role in autoimmune diabetes. From enrichment analysis, we found that there was a common genetic influence for both DNA methylation and T1D across the genome, implying that methylation could be either on the causal pathway to T1D or a non-causal biomarker of T1D genetic risk. Using data from a general population comprising blood samples taken at birth (n = 844), childhood (n = 846) and adolescence (n = 907), we then evaluated the associations between 64 top GWAS single nucleotide polymorphisms (SNPs) and DNA methylation levels at 55 non-HLA loci. We identified 95 proximal SNP-cytosine phosphate guanine (CpG) pairs ( cis ) and 1 distal SNP-CpG association ( trans ) consistently at birth, childhood, and adolescence. Combining genetic co-localization and Mendelian Randomization analysis, we provided evidence that at 5 loci, ITGB3BP , AFF3, PTPN2, CTSH and CTLA4 , DNA methylation is potentially mediating the genetic risk of T1D mainly by influencing local gene expression. [ABSTRACT FROM AUTHOR]
- Published
- 2018
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