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DNA methylation map...
DNA methylation mapping identifies gene regulatory effects in patients with systemic lupus erythematosus
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- Imgenberg-Kreuz, Juliana (author)
- Uppsala University,Uppsala universitet,Science for Life Laboratory, SciLifeLab,Molekylär medicin,Reumatologi,Uppsala Univ, Sweden
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- Almlöf, Jonas Carlsson (author)
- Uppsala University,Uppsala universitet,Molekylär medicin,Science for Life Laboratory, SciLifeLab,Uppsala Univ, Sweden
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- Leonard, Dag, 1975- (author)
- Uppsala University,Uppsala universitet,Reumatologi,Uppsala Univ, Sweden
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- Alexsson, Andrei (author)
- Lunds universitet,Uppsala University,Uppsala universitet,Reumatologi,Lund University, Skane University Hospital, Lund, Sweden,Uppsala Univ, Sweden,Lund Univ, Sweden,Lund SLE Research Group,Forskargrupper vid Lunds universitet,Lund University Research Groups
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- Nordmark, Gunnel (author)
- Uppsala University,Uppsala universitet,Reumatologi,Uppsala Univ, Sweden
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- Eloranta, Maija-Leena (author)
- Uppsala University,Uppsala universitet,Reumatologi,Uppsala Univ, Sweden
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- Rantapää-Dahlqvist, Solbritt (author)
- Umeå universitet,Reumatologi,Umeå University, Umeå, Sweden,Umea Univ, Sweden
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- Bengtsson, Anders A (author)
- Lund University, Skane University Hospital, Lund, Sweden
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- Jönsen, Andreas (author)
- Lund University,Lunds universitet,Lund SLE Research Group,Forskargrupper vid Lunds universitet,Lund University Research Groups,Skåne University Hospital
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- Padyukov, Leonid (author)
- Karolinska Institute,Karolinska Institutet,Karolinska Inst, Sweden,Karolinska University Hospital
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- Gunnarsson, Iva (author)
- Karolinska Institute,Karolinska Institutet,Karolinska Inst, Sweden,Karolinska University Hospital
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- Svenungsson, Elisabet (author)
- Karolinska Institute,Karolinska Institutet,Karolinska Inst, Sweden,Karolinska University Hospital
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- Sjöwall, Christopher (author)
- Linköping University,Linköpings universitet,Avdelningen för neuro- och inflammationsvetenskap,Medicinska fakulteten,Region Östergötland, Reumatologiska kliniken i Östergötland
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- Rönnblom, Lars (author)
- Uppsala University,Uppsala universitet,Reumatologi,Uppsala Univ, Sweden
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- Syvänen, Ann-Christine, 1950- (author)
- Uppsala University,Uppsala universitet,Molekylär epidemiologi,Science for Life Laboratory, SciLifeLab,Uppsala Univ, Sweden
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- Sandling, Johanna K. (author)
- Uppsala University,Uppsala universitet,Molekylär medicin,Reumatologi,Science for Life Laboratory, SciLifeLab,Uppsala Univ, Sweden; Uppsala Univ, Sweden
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(creator_code:org_t)
- 2018-02-01
- 2018
- English.
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In: Annals of the Rheumatic Diseases. - : BMJ. - 0003-4967 .- 1468-2060. ; 77:5, s. 736-743
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https://doi.org/10.1...
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https://urn.kb.se/re...
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https://doi.org/10.1...
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https://urn.kb.se/re...
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http://kipublication...
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https://urn.kb.se/re...
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https://lup.lub.lu.s...
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Abstract
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- 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.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Reumatologi och inflammation (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Rheumatology and Autoimmunity (hsv//eng)
Keyword
- gene polymorphism
- systemic lupus erythematosus
- gene polymorphism
- systemic lupus erythematosus
Publication and Content Type
- ref (subject category)
- art (subject category)
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Imgenberg-Kreuz, ...
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Almlöf, Jonas Ca ...
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Leonard, Dag, 19 ...
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Alexsson, Andrei
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Nordmark, Gunnel
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Eloranta, Maija- ...
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Rantapää-Dahlqvi ...
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Bengtsson, Ander ...
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Jönsen, Andreas
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Padyukov, Leonid
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Gunnarsson, Iva
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Svenungsson, Eli ...
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Sjöwall, Christo ...
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Rönnblom, Lars
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Syvänen, Ann-Chr ...
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Sandling, Johann ...
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- About the subject
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- MEDICAL AND HEALTH SCIENCES
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MEDICAL AND HEAL ...
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and Clinical Medicin ...
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and Rheumatology and ...
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Annals of the Rh ...
- By the university
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Uppsala University
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Umeå University
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Karolinska Institutet
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Linköping University
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Lund University