RT Journal Article
SR Electronic
T1 DNA methylation mapping identifies gene regulatory effects in patients with systemic lupus erythematosus
JF Annals of the Rheumatic Diseases
JO Ann Rheum Dis
FD BMJ Publishing Group Ltd and European League Against Rheumatism
SP 736
OP 743
DO 10.1136/annrheumdis-2017-212379
VO 77
IS 5
A1 Juliana Imgenberg-Kreuz
A1 Jonas Carlsson Almlöf
A1 Dag Leonard
A1 Andrei Alexsson
A1 Gunnel Nordmark
A1 Maija-Leena Eloranta
A1 Solbritt Rantapää-Dahlqvist
A1 Anders A Bengtsson
A1 Andreas Jönsen
A1 Leonid Padyukov
A1 Iva Gunnarsson
A1 Elisabet Svenungsson
A1 Christopher Sjöwall
A1 Lars Rönnblom
A1 Ann-Christine Syvänen
A1 Johanna K Sandling
YR 2018
UL http://ard.bmj.com/content/77/5/736.abstract
AB Objectives Systemic lupus erythematosus (SLE) is a chronic autoimmune condition with heterogeneous presentation and complex aetiology where DNA methylation changes are emerging as a contributing factor. In order to discover novel epigenetic associations and investigate their relationship to genetic risk for SLE, we analysed DNA methylation profiles in a large collection of patients with SLE and healthy individuals.Methods DNA extracted from blood from 548 patients with SLE and 587 healthy controls were analysed on the Illumina HumanMethylation 450 k BeadChip, which targets 485 000 CpG sites across the genome. Single nucleotide polymorphism (SNP) genotype data for 196 524 SNPs on the Illumina ImmunoChip from the same individuals were utilised for methylation quantitative trait loci (cis-meQTLs) analyses.Results We identified and replicated differentially methylated CpGs (DMCs) in SLE at 7245 CpG sites in the genome. The largest methylation differences were observed at type I interferon-regulated genes which exhibited decreased methylation in SLE. We mapped cis-meQTLs and identified genetic regulation of methylation levels at 466 of the DMCs in SLE. The meQTLs for DMCs in SLE were enriched for genetic association to SLE, and included seven SLE genome-wide association study (GWAS) loci: PTPRC (CD45), MHC-class III, UHRF1BP1, IRF5, IRF7, IKZF3 and UBE2L3. In addition, we observed association between genotype and variance of methylation at 20 DMCs in SLE, including at the HLA-DQB2 locus.Conclusions Our results suggest that several of the genetic risk variants for SLE may exert their influence on the phenotype through alteration of DNA methylation levels at regulatory regions of target genes.