Projects per year
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.
Original language | English |
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Pages (from-to) | 66-75 |
Number of pages | 10 |
Journal | Journal of Autoimmunity |
Volume | 93 |
Early online date | 29 Jun 2018 |
DOIs | |
Publication status | Published - 1 Sep 2018 |
Keywords
- DNA methylation
- Epigenetics
- Mendelian randomization
- Type 1 diabetes
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Projects
- 1 Finished
Equipment
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Illumina Array
Susan M Ring (Manager)
Bristol Population Health Science InstituteFacility/equipment: Facility
Profiles
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Professor Kathleen M Gillespie
- Bristol Medical School (THS) - Professor of Molecular Medicine
- Bristol Population Health Science Institute
- Infection and Immunity
- Diabetes and Metabolism
Person: Academic , Member
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Dr Gibran Hemani
- Bristol Medical School (PHS) - Senior Research Fellow
- Bristol Population Health Science Institute
- MRC Integrative Epidemiology Unit
Person: Academic , Member
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Professor Caroline L Relton
- Bristol Population Health Science Institute
- Bristol Medical School (PHS) - Professor of Epigenetic Epidemiology
- MRC Integrative Epidemiology Unit
- Cancer
Person: Academic , Member, Group lead