Identification of loci where DNA methylation potentially mediates genetic risk of type 1 diabetes.
J Autoimmun
; 93: 66-75, 2018 09.
Article
in En
| MEDLINE
| ID: mdl-30146008
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 (nâ¯=â¯844), childhood (nâ¯=â¯846) and adolescence (nâ¯=â¯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.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Genome, Human
/
CpG Islands
/
Quantitative Trait Loci
/
Epigenesis, Genetic
/
Diabetes Mellitus, Type 1
Type of study:
Clinical_trials
/
Diagnostic_studies
/
Etiology_studies
/
Observational_studies
/
Prognostic_studies
/
Risk_factors_studies
Limits:
Adolescent
/
Adult
/
Aged
/
Child
/
Female
/
Humans
/
Male
/
Middle aged
/
Newborn
Language:
En
Journal:
J Autoimmun
Journal subject:
ALERGIA E IMUNOLOGIA
Year:
2018
Document type:
Article