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  • 1. Adoue, Veronique
    et al.
    Schiavi, Alicia
    Light, Nicholas
    Carlsson Almlöf, Jonas
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular Medicine. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Lundmark, Per
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular Medicine. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Ge, Bing
    Kwan, Tony
    Caron, Maxime
    Rönnblom, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Rheumatology.
    Wang, Chuan
    Chen, Shu-Huang
    Goodall, Alison H
    Cambien, Francois
    Deloukas, Panos
    Ouwehand, Willem H
    Syvänen, Ann-Christine
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular Medicine. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Pastinen, Tomi
    Allelic expression mapping across cellular lineages to establish impact of non-coding SNPs2014In: Molecular Systems Biology, ISSN 1744-4292, E-ISSN 1744-4292, Vol. 10, no 10, p. 754-Article in journal (Refereed)
    Abstract [en]

    Most complex disease-associated genetic variants are located in non-coding regions and are therefore thought to be regulatory in nature. Association mapping of differential allelic expression (AE) is a powerful method to identify SNPs with direct cis-regulatory impact (cis-rSNPs). We used AE mapping to identify cis-rSNPs regulating gene expression in 55 and 63 HapMap lymphoblastoid cell lines from a Caucasian and an African population, respectively, 70 fibroblast cell lines, and 188 purified monocyte samples and found 40-60% of these cis-rSNPs to be shared across cell types. We uncover a new class of cis-rSNPs, which disrupt footprint-derived de novo motifs that are predominantly bound by repressive factors and are implicated in disease susceptibility through overlaps with GWAS SNPs. Finally, we provide the proof-of-principle for a new approach for genome-wide functional validation of transcription factor-SNP interactions. By perturbing NFκB action in lymphoblasts, we identified 489 cis-regulated transcripts with altered AE after NFκB perturbation. Altogether, we perform a comprehensive analysis of cis-variation in four cell populations and provide new tools for the identification of functional variants associated to complex diseases.

  • 2.
    Almlöf, Jonas Carlsson
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular Medicine. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Lundmark, Per
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular Medicine. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Lundmark, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular Medicine. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Ge, B.
    Maouche, S.
    Göring, H. H. H.
    Liljedahl, Ulrika
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular Medicine. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Enström, Camilla
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular Medicine. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Brocheton, J.
    Proust, C.
    Godefroy, T.
    Sambrook, J. G.
    Jolley, J.
    Crisp-Hihn, A.
    Foad, N.
    Lloyd-Jones, H.
    Stephens, J.
    Gwilliam, R.
    Rice, C. M.
    Hengstenberg, C.
    Samani, N. J.
    Erdmann, J.
    Schunkert, H.
    Pastinen, T.
    Deloukas, P.
    Goodall, A. H.
    Ouwehand, W. H.
    Cambien, F.
    Syvänen, Ann-Christine
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular Medicine. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Powerful Identification of Cis-regulatory SNPs in Human Primary Monocytes Using Allele-Specific Gene Expression2012In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 7, no 12, p. e52260-Article in journal (Refereed)
    Abstract [en]

    A large number of genome-wide association studies have been performed during the past five years to identify associations between SNPs and human complex diseases and traits. The assignment of a functional role for the identified disease-associated SNP is not straight-forward. Genome-wide expression quantitative trait locus (eQTL) analysis is frequently used as the initial step to define a function while allele-specific gene expression (ASE) analysis has not yet gained a wide-spread use in disease mapping studies. We compared the power to identify cis-acting regulatory SNPs (cis-rSNPs) by genome-wide allele-specific gene expression (ASE) analysis with that of traditional expression quantitative trait locus (eQTL) mapping. Our study included 395 healthy blood donors for whom global gene expression profiles in circulating monocytes were determined by Illumina BeadArrays. ASE was assessed in a subset of these monocytes from 188 donors by quantitative genotyping of mRNA using a genome-wide panel of SNP markers. The performance of the two methods for detecting cis-rSNPs was evaluated by comparing associations between SNP genotypes and gene expression levels in sample sets of varying size. We found that up to 8-fold more samples are required for eQTL mapping to reach the same statistical power as that obtained by ASE analysis for the same rSNPs. The performance of ASE is insensitive to SNPs with low minor allele frequencies and detects a larger number of significantly associated rSNPs using the same sample size as eQTL mapping. An unequivocal conclusion from our comparison is that ASE analysis is more sensitive for detecting cis-rSNPs than standard eQTL mapping. Our study shows the potential of ASE mapping in tissue samples and primary cells which are difficult to obtain in large numbers.

  • 3.
    Almlöf, Jonas Carlsson
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular Medicine. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Nystedt, Sara
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular Medicine. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Leonard, Dag
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Rheumatology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Eloranta, Maija-Leena
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Rheumatology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Grosso, Giorgia
    Karolinska Univ Hosp, Karolinska Inst, Dept Med, Rheumatol Unit,Rheumatol, S-17177 Stockholm, Sweden.
    Sjowall, Christopher
    Linkoping Univ, Div Neuro & Inflammat Sci, Dept Clin & Expt Med, Rheumatol, S-58183 Linkoping, Sweden.
    Bengtsson, Anders A.
    Lund Univ, Skane Univ Hosp, Dept Clin Sci, Rheumatol, S-22242 Lund, Sweden.
    Jonsen, Andreas
    Lund Univ, Skane Univ Hosp, Dept Clin Sci, Rheumatol, S-22242 Lund, Sweden.
    Gunnarsson, Iva
    Karolinska Univ Hosp, Karolinska Inst, Dept Med, Rheumatol Unit,Rheumatol, S-17177 Stockholm, Sweden.
    Svenungsson, Elisabet
    Karolinska Univ Hosp, Karolinska Inst, Dept Med, Rheumatol Unit,Rheumatol, S-17177 Stockholm, Sweden.
    Rönnblom, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Rheumatology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Sandling, Johanna K.
    Uppsala University, Science for Life Laboratory, SciLifeLab. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Rheumatology.
    Syvänen, Ann-Christine
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular Medicine. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Whole-genome sequencing identifies complex contributions to genetic risk by variants in genes causing monogenic systemic lupus erythematosus2019In: Human Genetics, ISSN 0340-6717, E-ISSN 1432-1203, Vol. 138, no 2, p. 141-150Article in journal (Refereed)
    Abstract [en]

    Systemic lupus erythematosus (SLE, OMIM 152700) is a systemic autoimmune disease with a complex etiology. The mode of inheritance of the genetic risk beyond familial SLE cases is currently unknown. Additionally, the contribution of heterozygous variants in genes known to cause monogenic SLE is not fully understood. Whole-genome sequencing of DNA samples from 71 Swedish patients with SLE and their healthy biological parents was performed to investigate the general genetic risk of SLE using known SLE GWAS risk loci identified using the ImmunoChip, variants in genes associated to monogenic SLE, and the mode of inheritance of SLE risk alleles in these families. A random forest model for predicting genetic risk for SLE showed that the SLE risk variants were mainly inherited from one of the parents. In the 71 patients, we detected a significant enrichment of ultra-rare (0.1%) missense and nonsense mutations in 22 genes known to cause monogenic forms of SLE. We identified one previously reported homozygous nonsense mutation in the C1QC (Complement C1q C Chain) gene, which explains the immunodeficiency and severe SLE phenotype of that patient. We also identified seven ultra-rare, coding heterozygous variants in five genes (C1S, DNASE1L3, DNASE1, IFIH1, and RNASEH2A) involved in monogenic SLE. Our findings indicate a complex contribution to the overall genetic risk of SLE by rare variants in genes associated with monogenic forms of SLE. The rare variants were inherited from the other parent than the one who passed on the more common risk variants leading to an increased genetic burden for SLE in the child. Higher frequency SLE risk variants are mostly passed from one of the parents to the offspring affected with SLE. In contrast, the other parent, in seven cases, contributed heterozygous rare variants in genes associated with monogenic forms of SLE, suggesting a larger impact of rare variants in SLE than hitherto reported.

  • 4.
    Almlöf, Jonas
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular Medicine. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Lundmark, Per
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular Medicine. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Lundmark, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular Medicine. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Ge, Bing
    Pastinen, Tomi
    Goodall, Alison H
    Cambien, François
    Deloukas, Panos
    Ouwehand, Willem H
    Syvänen, Ann-Christine
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular Medicine. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Single nucleotide polymorphisms with cis-regulatory effects on long non-coding transcripts in human primary monocytes2014In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 9, no 7, p. e102612-Article in journal (Refereed)
    Abstract [en]

    We applied genome-wide allele-specific expression analysis of monocytes from 188 samples. Monocytes were purified from white blood cells of healthy blood donors to detect cis-acting genetic variation that regulates the expression of long non-coding RNAs. We analysed 8929 regions harboring genes for potential long non-coding RNA that were retrieved from data from the ENCODE project. Of these regions, 60% were annotated as intergenic, which implies that they do not overlap with protein-coding genes. Focusing on the intergenic regions, and using stringent analysis of the allele-specific expression data, we detected robust cis-regulatory SNPs in 258 out of 489 informative intergenic regions included in the analysis. The cis-regulatory SNPs that were significantly associated with allele-specific expression of long non-coding RNAs were enriched to enhancer regions marked for active or bivalent, poised chromatin by histone modifications. Out of the lncRNA regions regulated by cis-acting regulatory SNPs, 20% (n = 52) were co-regulated with the closest protein coding gene. We compared the identified cis-regulatory SNPs with those in the catalog of SNPs identified by genome-wide association studies of human diseases and traits. This comparison identified 32 SNPs in loci from genome-wide association studies that displayed a strong association signal with allele-specific expression of non-coding RNAs in monocytes, with p-values ranging from 6.7×10-7 to 9.5×10-89. The identified cis-regulatory SNPs are associated with diseases of the immune system, like multiple sclerosis and rheumatoid arthritis.

  • 5.
    Carlsson Almlöf, Jonas
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular Medicine. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Alexsson, Andrei
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Rheumatology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Imgenberg-Kreuz, Juliana
    Uppsala University, Science for Life Laboratory, SciLifeLab. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular Medicine.
    Sylwan, Lina
    Karolinska Inst, Dept Biosci & Nutr, Sci Life Lab SciLifeLab, Solna, Sweden..
    Bäcklin, Christofer
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular Medicine. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Leonard, Dag
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Rheumatology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Nordmark, Gunnel
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Rheumatology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Tandre, Karolina
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Rheumatology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Eloranta, Maija-Leena
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Rheumatology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Padyukov, Leonid
    Karolinska Univ Hosp, Karolinska Inst, Dept Med, Rheumatol Unit, Stockholm, Sweden..
    Bengtsson, Christine
    Umea Univ, Dept Publ Hlth & Clin Med Rheumatol, Umea, Sweden..
    Jonsen, Andreas
    Lund Univ, Skane Univ Hosp, Dept Clin Sci, Rheumatol, Lund, Sweden..
    Dahlqvist, Solbritt Rantapaa
    Umea Univ, Dept Publ Hlth & Clin Med Rheumatol, Umea, Sweden..
    Sjowall, Christopher
    Linkoping Univ, Dept Clin & Expt Med, AIR Rheumatol, Linkoping, Sweden..
    Bengtsson, Anders A.
    Lund Univ, Skane Univ Hosp, Dept Clin Sci, Rheumatol, Lund, Sweden..
    Gunnarsson, Iva
    Karolinska Univ Hosp, Karolinska Inst, Dept Med, Rheumatol Unit, Stockholm, Sweden..
    Svenungsson, Elisabet
    Karolinska Univ Hosp, Karolinska Inst, Dept Med, Rheumatol Unit, Stockholm, Sweden..
    Rönnblom, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Rheumatology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Sandling, Johanna K.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular Medicine. Uppsala University, Science for Life Laboratory, SciLifeLab. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Rheumatology.
    Syvänen, Ann-Christine
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular Medicine. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Novel risk genes for systemic lupus erythematosus predicted by random forest classification2017In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 7, article id 6236Article in journal (Refereed)
    Abstract [en]

    Genome-wide association studies have identified risk loci for SLE, but a large proportion of the genetic contribution to SLE still remains unexplained. To detect novel risk genes, and to predict an individual's SLE risk we designed a random forest classifier using SNP genotype data generated on the "Immunochip" from 1,160 patients with SLE and 2,711 controls. Using gene importance scores defined by the random forest classifier, we identified 15 potential novel risk genes for SLE. Of them 12 are associated with other autoimmune diseases than SLE, whereas three genes (ZNF804A, CDK1, and MANF) have not previously been associated with autoimmunity. Random forest classification also allowed prediction of patients at risk for lupus nephritis with an area under the curve of 0.94. By allele-specific gene expression analysis we detected cis-regulatory SNPs that affect the expression levels of six of the top 40 genes designed by the random forest analysis, indicating a regulatory role for the identified risk variants. The 40 top genes from the prediction were overrepresented for differential expression in B and T cells according to RNA-sequencing of samples from five healthy donors, with more frequent over-expression in B cells compared to T cells.

  • 6.
    Imgenberg-Kreuz, Juliana
    et al.
    Uppsala University, Science for Life Laboratory, SciLifeLab. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular Medicine. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Rheumatology.
    Almlöf, Jonas Carlsson
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular Medicine. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Leonard, Dag
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Rheumatology.
    Alexsson, Andrei
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Rheumatology.
    Nordmark, Gunnel
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Rheumatology.
    Eloranta, Maija-Leena
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Rheumatology.
    Rantapää-Dahlqvist, Solbritt
    Umeå University, Umeå, Sweden.
    Bengtsson, Anders A
    Lund University, Skane University Hospital, Lund, Sweden.
    Jönsen, Andreas
    Lund University, Skane University Hospital, Lund, Sweden.
    Padyukov, Leonid
    Karolinska University Hospital, Stockholm, Sweden.
    Gunnarsson, Iva
    Karolinska University Hospital, Stockholm, Sweden.
    Svenungsson, Elisabet
    Karolinska University Hospital, Stockholm, Sweden.
    Sjöwall, Christopher
    Linköping University, Linköping, Sweden.
    Rönnblom, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Rheumatology.
    Syvänen, Ann-Christine
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular epidemiology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Sandling, Johanna K.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular Medicine. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Rheumatology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    DNA methylation mapping identifies gene regulatory effects in patients with systemic lupus erythematosus2018In: Annals of the Rheumatic Diseases, ISSN 0003-4967, E-ISSN 1468-2060, Vol. 77, no 5, p. 736-743Article in journal (Refereed)
    Abstract [en]

    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.

  • 7.
    Imgenberg-Kreuz, Juliana
    et al.
    Uppsala University, Science for Life Laboratory, SciLifeLab. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular Medicine. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Rheumatology.
    Almlöf, Jonas Carlsson
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular Medicine. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Leonard, Dag
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Rheumatology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Nordmark, Gunnel
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Rheumatology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Eloranta, Maija-Leena
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Rheumatology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Padyukov, Leonid
    Karolinska Univ Hosp, Karolinska Inst, Rheumatol Unit, Dept Med Solna, Stockholm, Sweden..
    Gunnarsson, Iva
    Karolinska Univ Hosp, Karolinska Inst, Rheumatol Unit, Dept Med Solna, Stockholm, Sweden..
    Svenungsson, Elisabet
    Karolinska Univ Hosp, Karolinska Inst, Rheumatol Unit, Dept Med Solna, Stockholm, Sweden..
    Sjowall, Christopher
    Linkoping Univ, Rheumatol AIR, Dept Clin & Expt Med, Linkoping, Sweden..
    Rönnblom, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Rheumatology.
    Syvänen, Ann-Christine
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular Medicine. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Sandling, Johanna K.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular Medicine. Uppsala University, Science for Life Laboratory, SciLifeLab. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Rheumatology.
    Treatment-Associated DNA Methylation Patterns in Systemic Lupus Erythematosus2017In: Arthritis & Rheumatology, ISSN 2326-5191, E-ISSN 2326-5205, Vol. 69, no S10, article id 2654Article in journal (Other academic)
  • 8.
    Imgenberg-Kreuz, Juliana
    et al.
    Uppsala University, Science for Life Laboratory, SciLifeLab. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Rheumatology.
    Carlsson Almlöf, Jonas
    Uppsala University, Science for Life Laboratory, SciLifeLab. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular Medicine.
    Leonard, Dag
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Rheumatology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Sjöwall, Christopher
    Linkoping Univ, Dept Clin & Expt Med, Div Neuro & Inflammat Sci, Rheumatol, Linkoping, Sweden.
    Syvänen, Ann-Christine
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular Medicine. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Rönnblom, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Rheumatology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Sandling, Johanna K.
    Uppsala University, Science for Life Laboratory, SciLifeLab. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Rheumatology.
    Nordmark, Gunnel
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Rheumatology. Uppsala University, Science for Life Laboratory, SciLifeLab. Uppsala Univ, Sect Rheumatol, Uppsala, Sweden;Uppsala Univ, Sci Life Lab, Dept Med Sci, Uppsala, Sweden.
    Shared and Unique Patterns of DNA Methylation in Systemic Lupus Erythematosus and Primary Sjogren's Syndrome2019In: Frontiers in Immunology, ISSN 1664-3224, E-ISSN 1664-3224, Vol. 10, article id 1686Article in journal (Refereed)
    Abstract [en]

    Objectives: To performa cross-comparative analysis of DNA methylation in patients with systemic lupus erythematosus (SLE), patients with primary Sjogren's syndrome (pSS), and healthy controls addressing the question of epigenetic sharing and aiming to detect disease-specific alterations. Methods: DNA extracted from peripheral blood from 347 cases with SLE, 100 cases with pSS, and 400 healthy controls were analyzed on the Human Methylation 450k array, targeting 485,000 CpG sites across the genome. A linear regression model including age, sex, and blood cell type distribution as covariates was fitted, and association p-values were Bonferroni corrected. A random forest machine learning classifier was designed for prediction of disease status based on DNA methylation data. Results: We established a combined set of 4,945 shared differentially methylated CpG sites (DMCs) in SLE and pSS compared to controls. In pSS, hypomethylation at type I interferon induced genes was mainly driven by patients who were positive for Ro/SSA and/or La/SSB autoantibodies. Analysis of differential methylation between SLE and pSS identified 2,244 DMCs with a majority of sites showing decreased methylation in SLE compared to pSS. The random forest classifier demonstrated good performance in discerning between disease status with an area under the curve (AUC) between 0.83 and 0.96. Conclusions: The majority of differential DNA methylation is shared between SLE and pSS, however, important quantitative differences exist. Our data highlight neutrophil dysregulation as a shared mechanism, emphasizing the role of neutrophils in the pathogenesis of systemic autoimmune diseases. The current study provides evidence for genes and molecular pathways driving common and disease-specific pathogenic mechanisms.

  • 9.
    Imgenberg-Kreuz, Juliana
    et al.
    Uppsala University, Science for Life Laboratory, SciLifeLab. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Rheumatology.
    Leonard, Dag
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Rheumatology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Carlsson Almlöf, Jonas
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular Medicine. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Rantapaa-Dahlqvist, S.
    Umea Univ, Dept Publ Hlth & Clin Med Rheumatol, Umea, Sweden.
    Bengtsson, A.
    Lund Univ, Dept Clin Sci, Rheumatol, Lund, Sweden.
    Jonsen, A.
    Lund Univ, Dept Clin Sci, Rheumatol, Lund, Sweden.
    Padyukov, L.
    Karolinska Inst, Dept Med Solna, Rheumatol Unit, Stockholm, Sweden.
    Gunnarsson, I.
    Karolinska Inst, Dept Med Solna, Rheumatol Unit, Stockholm, Sweden.
    Svenungsson, E.
    Karolinska Inst, Dept Med Solna, Rheumatol Unit, Stockholm, Sweden.
    Sjowall, C.
    Linkoping Univ, Rheumatol Div Neuro & Inflammat Sci, Dept Clin & Expt Med, Linkoping, Sweden.
    Syvänen, Ann-Christine
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular Medicine. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Rönnblom, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Rheumatology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Nordmark, Gunnel
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Rheumatology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Sandling, Johanna K.
    Uppsala University, Science for Life Laboratory, SciLifeLab. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Rheumatology.
    Shared and unique patterns of DNA methylation in primary Sjogren's syndrome and systemic lupus erythematosus2018In: Scandinavian Journal of Rheumatology, ISSN 0300-9742, E-ISSN 1502-7732, Vol. 47, p. 3-3Article in journal (Other academic)
  • 10.
    Imgenberg-Kreuz, Juliana
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular Medicine. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Sandling, Johanna K.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular Medicine. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Rheumatology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Almlöf, Jonas Carlsson
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular Medicine. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Nordlund, Jessica
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular Medicine. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Signer, Linnea
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Rheumatology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Norheim, Katrine B.
    Stavanger Univ Hosp, Dept Internal Med, Clin Immunol Unit, Stavanger, Norway..
    Omdal, Roald
    Stavanger Univ Hosp, Dept Internal Med, Clin Immunol Unit, Stavanger, Norway..
    Eloranta, Majia-Leena
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Rheumatology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Rönnblom, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Rheumatology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Syvanen, Ann-Christine
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular Medicine. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Nordmark, Gunnel
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Rheumatology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Hypomethylation in Enhancer and Promoter Regions of Interferon Regulated Genes in Multiple Tissues Is Associated with Primary Sjogren's Syndrome2015In: Arthritis & Rheumatology, ISSN 2326-5191, E-ISSN 2326-5205, Vol. 67, no Suppl. 10, article id 2100Article in journal (Other academic)
  • 11.
    Imgenberg-Kreuz, Juliana
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular Medicine. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Sandling, Johanna K.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Rheumatology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular Medicine. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Almlöf, Jonas Carlsson
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular Medicine. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Nordlund, Jessica
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular Medicine. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Signér, Linnea
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Rheumatology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Norheim, Katrine Braekke
    Stavanger Univ Hosp, Dept Internal Med, Clin Immunol Unit, Stavanger, Norway.
    Omdal, Roald
    Stavanger Univ Hosp, Dept Internal Med, Clin Immunol Unit, Stavanger, Norway.
    Rönnblom, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Rheumatology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Eloranta, Maija-Leena
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Rheumatology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Syvänen, Ann-Christine
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular Medicine. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Nordmark, Gunnel
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Rheumatology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Genome-wide DNA methylation analysis in multiple tissues in primary Sjögren's syndrome reveals regulatory effects at interferon-induced genes2016In: Annals of the Rheumatic Diseases, ISSN 0003-4967, E-ISSN 1468-2060, Vol. 75, no 11, p. 2029-2036Article in journal (Refereed)
    Abstract [en]

    OBJECTIVES: Increasing evidence suggests an epigenetic contribution to the pathogenesis of autoimmune diseases, including primary Sjögren's Syndrome (pSS). The aim of this study was to investigate the role of DNA methylation in pSS by analysing multiple tissues from patients and controls.

    METHODS: Genome-wide DNA methylation profiles were generated using HumanMethylation450K BeadChips for whole blood, CD19+ B cells and minor salivary gland biopsies. Gene expression was analysed in CD19+ B cells by RNA-sequencing. Analysis of genetic regulatory effects on DNA methylation at known pSS risk loci was performed.

    RESULTS: We identified prominent hypomethylation of interferon (IFN)-regulated genes in whole blood and CD19+ B cells, including at the genes MX1, IFI44L and PARP9, replicating previous reports in pSS, as well as identifying a large number of novel associations. Enrichment for genomic overlap with histone marks for enhancer and promoter regions was observed. We showed for the first time that hypomethylation of IFN-regulated genes in pSS B cells was associated with their increased expression. In minor salivary gland biopsies we observed hypomethylation of the IFN-induced gene OAS2. Pathway and disease analysis resulted in enrichment of antigen presentation, IFN signalling and lymphoproliferative disorders. Evidence for genetic control of methylation levels at known pSS risk loci was observed.

    CONCLUSIONS: Our study highlights the role of epigenetic regulation of IFN-induced genes in pSS where replication is needed for novel findings. The association with altered gene expression suggests a functional mechanism for differentially methylated CpG sites in pSS aetiology.

  • 12.
    Imgenberg-Kreuz, Juliana
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular Medicine. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Sandling, Johanna K.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Rheumatology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Carlsson Almlöf, Jonas
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular Medicine. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Omdal, Roald
    Norheim, Katrine Braekke
    Eloranta, Maija-Leena
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Rheumatology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Rönnblom, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Rheumatology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Syvänen, Ann-Christine
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Geriatrics. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Nordmark, Gunnel
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Rheumatology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Genome-Wide Analysis of DNA Methylation Profiles in Multiple Tissues in Primary Sjogren's Syndrome2015In: Scandinavian Journal of Immunology, ISSN 0300-9475, E-ISSN 1365-3083, Vol. 81, no 5, p. 412-412Article in journal (Other academic)
  • 13.
    Langefeld, Carl D.
    et al.
    Wake Forest Sch Med, Ctr Publ Hlth Genom, Winston Salem, NC 27101 USA.;Wake Forest Sch Med, Dept Biostat Sci, Winston Salem, NC 27101 USA..
    Ainsworth, Hannah C.
    Wake Forest Sch Med, Ctr Publ Hlth Genom, Winston Salem, NC 27101 USA.;Wake Forest Sch Med, Dept Biostat Sci, Winston Salem, NC 27101 USA..
    Graham, Deborah S. Cunninghame
    Kings Coll London, Guys Hosp, Div Genet & Mol Med & Immunol Infect & Inflammato, London SE1 9RT, England..
    Kelly, Jennifer A.
    Oklahoma Med Res Fdn, Arthrit & Clin Immunol Res Program, Oklahoma City, OK 73104 USA..
    Comeau, Mary E.
    Wake Forest Sch Med, Ctr Publ Hlth Genom, Winston Salem, NC 27101 USA.;Wake Forest Sch Med, Dept Biostat Sci, Winston Salem, NC 27101 USA..
    Marion, Miranda C.
    Wake Forest Sch Med, Ctr Publ Hlth Genom, Winston Salem, NC 27101 USA.;Wake Forest Sch Med, Dept Biostat Sci, Winston Salem, NC 27101 USA..
    Howard, Timothy D.
    Wake Forest Sch Med, Ctr Publ Hlth Genom, Winston Salem, NC 27101 USA.;Wake Forest Sch Med, Ctr Human Genom & Personalized Med Res, Winston Salem, NC 27101 USA..
    Ramos, Paula S.
    Med Univ S Carolina, Dept Publ Hlth Sci, Charleston, SC 29425 USA.;Med Univ South Carolina, Dept Med, Charleston, SC 29425 USA..
    Croker, Jennifer A.
    UAB Sch Med, Div Clin Immunol & Rheumatol, Birmingham, AL 35294 USA..
    Morris, David L.
    Kings Coll London, Guys Hosp, Div Genet & Mol Med & Immunol Infect & Inflammato, London SE1 9RT, England..
    Sandling, Johanna K.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular Medicine. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Carlsson Almlöf, Jonas
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular Medicine. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Acevedo-Vasquez, Eduardo M.
    Univ Nacl Mayor San Marcos, Fac Med, Dept Reumatol, Lima 15081, Peru..
    Alarcon, Graciela S.
    Babini, Alejandra M.
    Hosp Italiano Cordoba, Cordoba, Argentina..
    Baca, Vicente
    Hosp Pediat Mexico City, Ctr Med Nacl Siglo XXI, Inst Mexicano Seguro Social, Mexico City 06720, DF, Mexico..
    Bengtsson, Anders A.
    Lund Univ, Dept Clin Sci, Rheumatol, S-22362 Lund, Sweden..
    Berbotto, Guillermo A.
    Hosp Eva Peron, Granadero Baigorria, Argentina..
    Bijl, Marc
    Martini Hosp, Dept Internal Med & Rheumatol, NL-9728 NT Groningen, Netherlands..
    Brown, Elizabeth E.
    Brunner, Hermine I.
    Cincinnati Childrens Hosp Med Ctr, Dept Pediat, Div Rheumatol, Cincinnati, OH 45229 USA.;Univ Cincinnati, Cincinnati, OH 45229 USA..
    Cardiel, Mario H.
    Ctr Invest Clin Morelia, Morelia, Michoacan, Mexico..
    Catoggio, Luis
    Hosp Italiano Buenos Aires, RA-1181 Buenos Aires, DF, Argentina..
    Cervera, Ricard
    Univ Barcelona, Hosp Clin, Dept Autoimmune Dis, Barcelona 08007, Catalonia, Spain..
    Cucho-Venegas, Jorge M.
    Univ Nacl Mayor San Marcos, Fac Med, Dept Reumatol, Lima 15081, Peru..
    Dahlqvist, Solbritt Rantapaa
    Umea Univ, Dept Publ Hlth & Clin Med, Div Rheumatol, S-90187 Umea, Sweden..
    D'Alfonso, Sandra
    Univ Piemonte Orientale, Dept Hlth Sci & Inst Res Autoimmune Dis IRCAD, I-28100 Novara, Italy..
    Da Silva, Berta Martins
    Univ Porto, Inst Ciencias Biomed Abel Salaza, Unidade Multidisciplinar Invest Biomed, P-4099003 Oporto, Portugal..
    de la Rua Figueroa, Inigo
    Hosp Univ Gran Canaria Dr Negrin, Dept Rheumatol, Las Palmas Gran Canaria 35010, Spain..
    Doria, Andrea
    Univ Padua, Dept Med DIMED, Div Rheumatol, I-35122 Padua, Italy..
    Edberg, Jeffrey C.
    UAB Sch Med, Div Clin Immunol & Rheumatol, Birmingham, AL 35294 USA..
    Endreffy, Emoke
    Univ Szeged, Fac Med, Albert Szent Gyorgyi Med Ctr, Dept Pediat, H-6720 Szeged, Hungary.;Univ Szeged, Fac Med, Albert Szent Gyorgyi Med Ctr, Child Hlth Ctr, H-6720 Szeged, Hungary..
    Esquivel-Valerio, Jorge A.
    Hosp Univ Dr Jose Eleuterio Gonzalez Univ Autonom, Monterrey 64020, Mexico..
    Fortin, Paul R.
    Univ Laval, CHU Quebec, Quebec City, PQ G1R 2JG, Canada..
    Freedman, Barry I.
    Wake Forest Sch Med, Ctr Publ Hlth Genom, Winston Salem, NC 27101 USA.;Wake Forest Sch Med, Dept Biostat Sci, Winston Salem, NC 27101 USA.;Wake Forest Sch Med, Sect Nephrol, Winston Salem, NC 27101 USA..
    Frostegard, Johan
    Karolinska Inst, Inst Environm Med, Unit Immunol & Chron Dis, S-17177 Stockholm, Sweden..
    Garcia, Mercedes A.
    Hosp Interzonal Gen Agudos Gen San Martin, Div Rheumatol, RA-1900 La Plata, Buenos Aires, Argentina..
    Garcia de la Torre, Ignacio
    Univ Guadalajara, Dept Fisiol, Guadalajara, Jalisco 44100, Mexico..
    Gilkeson, Gary S.
    Med Univ South Carolina, Dept Med, Charleston, SC 29425 USA..
    Gladman, Dafna D.
    Toronto Western Hosp, Krembil Res Inst, Ctr Prognosis Studies Rheumat Dis, Toronto, ON M5T 2S8, Canada..
    Gunnarsson, Iva
    Karolinska Univ Hosp, Karolinska Inst, Dept Med Solna, Rheumatol Unit, S-17176 Stockholm, Sweden..
    Guthridge, Joel M.
    Oklahoma Med Res Fdn, Arthrit & Clin Immunol Res Program, Oklahoma City, OK 73104 USA..
    Huggins, Jennifer L.
    Cincinnati Childrens Hosp Med Ctr, Dept Pediat, Div Rheumatol, Cincinnati, OH 45229 USA.;Univ Cincinnati, Cincinnati, OH 45229 USA..
    James, Judith A.
    Hosp Eva Peron, Granadero Baigorria, Argentina.;Univ Oklahoma, Hlth Sci Ctr, Dept Med, Oklahoma City, OK 73104 USA.;Univ Oklahoma, Hlth Sci Ctr, Dept Pathol, Oklahoma City, OK 73104 USA..
    Kallenberg, Cees G. M.
    Univ Med Ctr Groningen, Univ Groningen, Dept Rheumatol & Clin Immunol, NL-9713 GZ Groningen, Netherlands..
    Kamen, Diane L.
    Karp, David R.
    Univ Texas Southwestern Med Ctr Dallas, Dept Immunol, Dallas, TX 75235 USA..
    Kaufman, Kenneth M.
    Cincinnati Childrens Hosp Med Ctr, CAGE, Dept Pediat, Cincinnati, OH 45229 USA..
    Kottyan, Leah C.
    Cincinnati Childrens Hosp Med Ctr, CAGE, Dept Pediat, Cincinnati, OH 45229 USA..
    Kovacs, Laszlo
    Univ Szeged, Albert Szent Gyorgyi Med Ctr, Dept Rheumatol, H-6720 Szeged, Hungary..
    Laustrup, Helle
    Odense Univ Hosp, Dept Rheumatol, DK-5000 Odense, Denmark..
    Lauwerys, Bernard R.
    Catholic Univ Louvain, Clin Univ St Luc, Rheumatol, B-1348 Louvain La Neuve, Belgium.;Catholic Univ Louvain, Inst Rech Expt & Clin, B-1348 Louvain La Neuve, Belgium..
    Li, Quan-Zhen
    Univ Texas Southwestern Med Ctr Dallas, Dept Immunol, Dallas, TX 75235 USA..
    Maradiaga-Cecena, Marco A.
    Hosp Gen Culiacan, Sinaloa 80220, Mexico..
    Martin, Javier
    CSIC, Inst Parasitol & Biomed Lopez Neyra, Granada 18100, Spain..
    McCune, Joseph M.
    Univ Michigan, Med Ctr, Ann Arbor, MI 48103 USA..
    McWilliams, David R.
    Wake Forest Sch Med, Ctr Publ Hlth Genom, Winston Salem, NC 27101 USA.;Wake Forest Sch Med, Dept Biostat Sci, Winston Salem, NC 27101 USA..
    Merrill, Joan T.
    Oklahoma Med Res Fdn, Arthrit & Clin Immunol Res Program, Oklahoma City, OK 73104 USA..
    Miranda, Pedro
    Ctr Estudios Reumatol, Santiago 7500000, Chile..
    Moctezuma, Jose F.
    Hosp Gen Mexico City, Dept Reumatol, Mexico City 06726, DF, Mexico..
    Nath, Swapan K.
    Oklahoma Med Res Fdn, Arthrit & Clin Immunol Res Program, Oklahoma City, OK 73104 USA..
    Niewold, Timothy B.
    Mayo Clin, Dept Rheumatol, Rochester, MN 94158 USA..
    Orozco, Lorena
    Inst Nacl Med Genom INMEGEN, Mexico City 14610, DF, Mexico..
    Ortego-Centeno, Norberto
    Hosp Univ San Cecilio, UGC Med Interna, Unidad Enfermedades Autoimmunes Sistem, Granada 18007, Spain..
    Petri, Michelle
    Johns Hopkins Univ, Sch Med, Dept Med, Div Rheumatol, Baltimore, MD 21218 USA..
    Pineau, Christian A.
    McGill Univ, Div Rheumatol, Montreal, PQ H3A 0G4, Canada..
    Pons-Estel, Bernardo A.
    Sanatorio Parque, Dept Rheumatol, Rosario, Santa Fe, Argentina..
    Pope, Janet
    Univ Western Ontario, London, ON M5T 2S8, Canada..
    Raj, Prithvi
    Univ Texas Southwestern Med Ctr Dallas, Dept Immunol, Dallas, TX 75235 USA..
    Ramsey-Goldman, Rosalind
    Northwestern Univ, Feinberg Sch Med, Div Rheumatol, Chicago, IL 60611 USA..
    Reveille, John D.
    Univ Texas Hlth Sci Ctr Houston UTHealth, Med Sch, Houston, TX 77030 USA..
    Russell, Laurie P.
    Wake Forest Sch Med, Ctr Publ Hlth Genom, Winston Salem, NC 27101 USA.;Wake Forest Sch Med, Dept Biostat Sci, Winston Salem, NC 27101 USA..
    Sabio, Jose M.
    Hosp Univ Virgen de las Nieves, Granada 18014, Spain..
    Aguilar-Salinas, Carlos A.
    Inst Nacl Ciencias Med & Nutr Salvador Zubiran, Dept Endocrinol & Metab, Vasco Quiroga 15, Mexico City 14080, DF, Mexico..
    Scherbarth, Hugo R.
    Autoinmunes HIGA Dr Alende Mar Plata, Unidad Reumatol & Enfermedades, Buenos Aires, DF, Argentina..
    Scorza, Raffaella
    Fdn IRCCS CaGranda Osped Ma Repiore Policlin, Referral Ctr Syst Autoimmune Dis, I-20122 Milan, Italy.;Univ Milan, I-20122 Milan, Italy..
    Seldin, Michael F.
    UC Davis Sch Med, Dept Biochem & Mol Med, Sacramento, CA 95616 USA..
    Sjowall, Christopher
    Linkoping Univ, Dept Clin & Expt Med, Rheumatol Div Neuro & Inflammat Sci, S-58183 Linkoping, Sweden..
    Svenungsson, Elisabet
    Karolinska Univ Hosp, Karolinska Inst, Dept Med Solna, Rheumatol Unit, S-17176 Stockholm, Sweden..
    Thompson, Susan D.
    Cincinnati Childrens Hosp Med Ctr, CAGE, Dept Pediat, Cincinnati, OH 45229 USA..
    Toloza, Sergio M. A.
    Minist Hlth, Catamarca, Argentina..
    Truedsson, Lennart
    Lund Univ, Dept Lab Med, Sect Microbiol Immunol & Glycobiol, S-22100 Lund, Sweden..
    Tusie-Luna, Teresa
    UNAM Inst Nacl Ciencias Med & Nutr Salvador Zubir, Inst Invest Biomed, Unidad Biol Mol & Med Genom, Mexico City 14080, DF, Mexico..
    Vasconcelos, Carlos
    Univ Porto, Hosp Santo Antonio, P-4099003 Oporto, Portugal..
    Vila, Luis M.
    Univ Puerto Rico, Sch Med, San Juan, PR 00936 USA..
    Wallace, Daniel J.
    Cedars Sinai Med Ctr, Dept Med, Los Angeles, CA 90048 USA..
    Weisman, Michael H.
    Cedars Sinai Med Ctr, Dept Med, Los Angeles, CA 90048 USA..
    Wither, Joan E.
    Toronto Western Hosp, Krembil Res Inst, Ctr Prognosis Studies Rheumat Dis, Toronto, ON M5T 2S8, Canada..
    Bhangale, Tushar
    Genentech Inc, Human Genet, South San Francisco, CA 94080 USA..
    Oksenberg, Jorge R.
    Univ Calif San Francisco, Dept Neurol, San Francisco, CA 94158 USA.;Univ Calif San Francisco, Inst Human Genet, San Francisco, CA 94158 USA..
    Rioux, John D.
    Univ Montreal, Montreal, PQ H1T 1C8, Canada.;Montreal Heart Inst, Montreal, PQ H1T 1C8, Canada..
    Gregersen, Peter K.
    Feinstein Inst Med Res, Ctr Genom Human Genet, Manhasset, NY 11030 USA..
    Syvänen, Ann-Christine
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular Medicine. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Rönnblom, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Rheumatology.
    Criswell, Lindsey A.
    UCSF Sch Med, Rosalind Russell Ephraim P Engleman Rheumatol Res, Div Rheumatol, San Francisco, CA 94158 USA..
    Jacob, Chaim O.
    Keck Sch Med USC, Los Angeles, CA 90033 USA..
    Sivils, Kathy L.
    Oklahoma Med Res Fdn, Arthrit & Clin Immunol Res Program, Oklahoma City, OK 73104 USA..
    Tsao, Betty P.
    Med Univ South Carolina, Dept Med, Charleston, SC 29425 USA..
    Schanberg, Laura E.
    Duke Univ, Dept Pediat, Durham, NC 27708 USA..
    Behrens, Timothy W.
    Genentech Inc, Human Genet, South San Francisco, CA 94080 USA..
    Silverman, Earl D.
    Hosp Sick Children, Res Inst, Dept Pediat, Toronto, ON M5G 1X8, Canada.;Hosp Sick Children, Res Inst, Inst Med Sci, Toronto, ON M5G 1X8, Canada.;Univ Toronto, Toronto, ON M5G 1X8, Canada..
    Alarcon-Riquelme, Marta E.
    Oklahoma Med Res Fdn, Arthrit & Clin Immunol Res Program, Oklahoma City, OK 73104 USA.;Univ Granada, Pfizer, Junta De Andalucia Ctr Genom & Oncol Res GENYO, Granada 18007, Spain.;Karolinska Inst, Unit Inst Environm Med, S-17177 Solnavagen, Sweden..
    Kimberly, Robert P.
    UAB Sch Med, Div Clin Immunol & Rheumatol, Birmingham, AL 35294 USA..
    Harley, John B.
    Cincinnati Childrens Hosp Med Ctr, CAGE, Dept Pediat, Cincinnati, OH 45229 USA..
    Wakeland, Edward K.
    Univ Texas Southwestern Med Ctr Dallas, Dept Immunol, Dallas, TX 75235 USA..
    Graham, Robert R.
    Genentech Inc, Human Genet, South San Francisco, CA 94080 USA..
    Gaffney, Patrick M.
    Oklahoma Med Res Fdn, Arthrit & Clin Immunol Res Program, Oklahoma City, OK 73104 USA..
    Vyse, Timothy J.
    Kings Coll London, Guys Hosp, Div Genet & Mol Med & Immunol Infect & Inflammato, London SE1 9RT, England..
    Transancestral mapping and genetic load in systemic lupus erythematosus2017In: Nature Communications, ISSN 2041-1723, E-ISSN 2041-1723, Vol. 8, article id 16021Article in journal (Refereed)
    Abstract [en]

    Systemic lupus erythematosus (SLE) is an autoimmune disease with marked gender and ethnic disparities. We report a large transancestral association study of SLE using Immunochip genotype data from 27,574 individuals of European (EA), African (AA) and Hispanic Amerindian (HA) ancestry. We identify 58 distinct non-HLA regions in EA, 9 in AA and 16 in HA (similar to 50% of these regions have multiple independent associations); these include 24 novel SLE regions (P < 5 x 10(-8)), refined association signals in established regions, extended associations to additional ancestries, and a disentangled complex HLA multigenic effect. The risk allele count (genetic load) exhibits an accelerating pattern of SLE risk, leading us to posit a cumulative hit hypothesis for autoimmune disease. Comparing results across the three ancestries identifies both ancestry-dependent and ancestry-independent contributions to SLE risk. Our results are consistent with the unique and complex histories of the populations sampled, and collectively help clarify the genetic architecture and ethnic disparities in SLE.

  • 14. Lappalainen, Tuuli
    et al.
    Sammeth, Michael
    Friedländer, Marc R
    't Hoen, Peter A C
    Monlong, Jean
    Rivas, Manuel A
    Gonzàlez-Porta, Mar
    Kurbatova, Natalja
    Griebel, Thasso
    Ferreira, Pedro G
    Barann, Matthias
    Wieland, Thomas
    Greger, Liliana
    van Iterson, Maarten
    Almlöf, Jonas
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular Medicine. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Ribeca, Paolo
    Pulyakhina, Irina
    Esser, Daniela
    Giger, Thomas
    Tikhonov, Andrew
    Sultan, Marc
    Bertier, Gabrielle
    Macarthur, Daniel G
    Lek, Monkol
    Lizano, Esther
    Buermans, Henk P J
    Padioleau, Ismael
    Schwarzmayr, Thomas
    Karlberg, Olof
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular Medicine. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Ongen, Halit
    Kilpinen, Helena
    Beltran, Sergi
    Gut, Marta
    Kahlem, Katja
    Amstislavskiy, Vyacheslav
    Stegle, Oliver
    Pirinen, Matti
    Montgomery, Stephen B
    Donnelly, Peter
    McCarthy, Mark I
    Flicek, Paul
    Strom, Tim M
    Lehrach, Hans
    Schreiber, Stefan
    Sudbrak, Ralf
    Carracedo, Angel
    Antonarakis, Stylianos E
    Häsler, Robert
    Syvänen, Ann-Christine
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular Medicine. Uppsala University, Science for Life Laboratory, SciLifeLab.
    van Ommen, Gert-Jan
    Brazma, Alvis
    Meitinger, Thomas
    Rosenstiel, Philip
    Guigó, Roderic
    Gut, Ivo G
    Estivill, Xavier
    Dermitzakis, Emmanouil T
    Transcriptome and genome sequencing uncovers functional variation in humans2013In: Nature, ISSN 0028-0836, E-ISSN 1476-4687, Vol. 501, no 7468, p. 506-511Article in journal (Refereed)
    Abstract [en]

    Genome sequencing projects are discovering millions of genetic variants in humans, and interpretation of their functional effects is essential for understanding the genetic basis of variation in human traits. Here we report sequencing and deep analysis of messenger RNA and microRNA from lymphoblastoid cell lines of 462 individuals from the 1000 Genomes Project-the first uniformly processed high-throughput RNA-sequencing data from multiple human populations with high-quality genome sequences. We discover extremely widespread genetic variation affecting the regulation of most genes, with transcript structure and expression level variation being equally common but genetically largely independent. Our characterization of causal regulatory variation sheds light on the cellular mechanisms of regulatory and loss-of-function variation, and allows us to infer putative causal variants for dozens of disease-associated loci. Altogether, this study provides a deep understanding of the cellular mechanisms of transcriptome variation and of the landscape of functional variants in the human genome.

  • 15.
    Lindqvist, C. Mårten
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular Medicine. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Lundmark, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular Medicine. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Nordlund, Jessica
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular Medicine. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Freyhult, Eva
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cancer Pharmacology and Computational Medicine. Uppsala University, Science for Life Laboratory, SciLifeLab. Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Cell and Molecular Biology, The Linnaeus Centre for Bioinformatics.
    Ekman, Diana
    Stockholm Univ, Dept Biochem & Biophys, Sci Life Lab, Stockholm, Sweden..
    Almlöf, Jonas Carlsson
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular Medicine. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Raine, Amanda
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular Medicine. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Övernäs, Elin
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular Medicine. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Abrahamsson, Jonas
    Queen Silvia Childrens Hosp, Dept Pediat, Gothenburg, Sweden..
    Frost, Britt-Marie
    Univ Childrens Hosp, Dept Womens & Childrens Hlth, Uppsala, Sweden..
    Grander, Dan
    Karolinska Inst, Dept Oncol Pathol, Stockholm, Sweden..
    Heyman, Mats
    Karolinska Univ Hosp, Astrid Lindgren Childrens Hosp, Dept Women & Child Hlth, Childhood Canc Res Unit, Stockholm, Sweden..
    Palle, Josefine
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular Medicine. Uppsala University, Science for Life Laboratory, SciLifeLab. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Pediatrics. Uppsala Univ, Dept Med Sci, Mol Med & Sci Life Lab, Uppsala, Sweden.;Univ Childrens Hosp, Dept Womens & Childrens Hlth, Uppsala, Sweden..
    Forestier, Erik
    Umea Univ, Dept Med Biosci, Umea, Sweden..
    Lönnerholm, Gudmar
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Pediatrics.
    Berglund, Eva C.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular Medicine. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Syvänen, Ann-Christine
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular Medicine. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Deep targeted sequencing in pediatric acute lymphoblastic leukemia unveils distinct mutational patterns between genetic subtypes and novel relapse-associated genes2016In: OncoTarget, ISSN 1949-2553, E-ISSN 1949-2553, Vol. 7, no 39, p. 64071-64088Article in journal (Refereed)
    Abstract [en]

    To characterize the mutational patterns of acute lymphoblastic leukemia (ALL) we performed deep next generation sequencing of 872 cancer genes in 172 diagnostic and 24 relapse samples from 172 pediatric ALL patients. We found an overall greater mutational burden and more driver mutations in T-cell ALL (T-ALL) patients compared to B-cell precursor ALL (BCP-ALL) patients. In addition, the majority of the mutations in T-ALL had occurred in the original leukemic clone, while most of the mutations in BCP-ALL were subclonal. BCP-ALL patients carrying any of the recurrent translocations ETV6-RUNX1, BCR-ABL or TCF3-PBX1 harbored few mutations in driver genes compared to other BCP-ALL patients. Specifically in BCP-ALL, we identified ATRX as a novel putative driver gene and uncovered an association between somatic mutations in the Notch signaling pathway at ALL diagnosis and increased risk of relapse. Furthermore, we identified EP300, ARID1A and SH2B3 as relapse-associated genes. The genes highlighted in our study were frequently involved in epigenetic regulation, associated with germline susceptibility to ALL, and present in minor subclones at diagnosis that became dominant at relapse. We observed a high degree of clonal heterogeneity and evolution between diagnosis and relapse in both BCP-ALL and T-ALL, which could have implications for the treatment efficiency.

  • 16.
    Marincevic-Zuniga, Yanara
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular Medicine. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Nystedt, Sara
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular Medicine. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Nilsson, Sara
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular Medicine. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Almlöf, Jonas Carlsson
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular Medicine. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Lilljebjörn, Henrik
    Fioretos, Thoas
    Flaegstad, Trond
    Forestier, Erik
    Heyman, Mats
    Kanerva, Jukka
    Schmiegelow, Kjeld
    Lönnerholm, Gudmar
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Research group (Dept. of women´s and children´s health), Neuropediatrics/Paediatric oncology.
    Nordlund, Jessica
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular Medicine. Uppsala University, Science for Life Laboratory, SciLifeLab.
    DNA methylation classification in combination with RNA-sequencing for subtype discovery in pediatric B-cell precursor acute lymphoblastic leukemiaManuscript (preprint) (Other academic)
  • 17.
    Marzouka, Nour-al-dain
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular Medicine.
    Nordlund, Jessica
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular Medicine.
    Bäcklin, Christofer L.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular Medicine. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cancer Pharmacology and Computational Medicine.
    Lönnerholm, Gudmar
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Pediatrics.
    Syvänen, Ann-Christine
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular Medicine.
    Almlöf, Jonas Carlsson
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular Medicine.
    CopyNumber450kCancer: baseline correction for accurate copy number calling from the 450k methylation array2016In: Bioinformatics, ISSN 1367-4803, E-ISSN 1367-4811, Vol. 32, no 7, p. 1080-1082Article in journal (Refereed)
    Abstract [en]

    The Illumina Infinium HumanMethylation450 BeadChip (450k) is widely used for the evaluation of DNA methylation levels in large-scale datasets, particularly in cancer. The 450k design allows copy number variant (CNV) calling using existing bioinformatics tools. However, in cancer samples, numerous large-scale aberrations cause shifting in the probe intensities and thereby may result in erroneous CNV calling. Therefore, a baseline correction process is needed. We suggest the maximum peak of probe segment density to correct the shift in the intensities in cancer samples.

  • 18.
    Nordmark, Gunnel
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Rheumatology.
    Imgenberg-Kreuz, Juliana
    Uppsala University, Science for Life Laboratory, SciLifeLab. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular Medicine.
    Almlöf, Jonas Carlsson
    Uppsala University, Science for Life Laboratory, SciLifeLab. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular Medicine.
    Nordlund, Jessica
    Uppsala University, Science for Life Laboratory, SciLifeLab. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular Medicine.
    Omdal, Roald
    Norheim, Katrine B.
    Eloranta, Maija-Leena
    Uppsala University, Science for Life Laboratory, SciLifeLab. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Rheumatology.
    Rönnblom, Lars
    Uppsala University, Science for Life Laboratory, SciLifeLab. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Rheumatology.
    Sandling, Johanna K.
    Uppsala University, Science for Life Laboratory, SciLifeLab. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular Medicine.
    Genome-Wide DNA Methylation Analysis of CD19+B Cells in Primary Sjogren's Syndrome2014In: Arthritis & Rheumatology, ISSN 2326-5191, Vol. 66, no S10, p. S1303-S1303, article id 2980Article in journal (Other academic)
  • 19.
    Sandling, Johanna K.
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular Medicine. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Imgenberg-Kreuz, Juliana
    Uppsala University, Science for Life Laboratory, SciLifeLab. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular Medicine.
    Carlsson Almlöf, Jonas
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular Medicine. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Nordmark, Gunnel
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Rheumatology.
    Eloranta, Maija-Leena
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Rheumatology.
    Padyukov, L.
    Karolinska Inst, Karolinska Univ Hosp, Dept Med, Rheumatol Unit, Stockholm, Sweden..
    Gunnarsson, I.
    Karolinska Inst, Karolinska Univ Hosp, Dept Med, Rheumatol Unit, Stockholm, Sweden..
    Svenungsson, E.
    Karolinska Inst, Karolinska Univ Hosp, Dept Med, Rheumatol Unit, Stockholm, Sweden..
    Sjowall, C.
    Linkoping Univ, Dept Clin & Expt Med, Rheumatol AIR, Linkoping, Sweden..
    Rönnblom, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Rheumatology.
    Syvänen, Ann-Christine
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular Medicine. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Genome-wide analysis of DNA methylation in systemic lupus erythematosus2015In: Clinical and Experimental Rheumatology, ISSN 0392-856X, E-ISSN 1593-098X, Vol. 33, no 3, p. S74-S74Article in journal (Other academic)
  • 20. 't Hoen, Peter A C
    et al.
    Friedländer, Marc R
    Almlöf, Jonas
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular Medicine. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Sammeth, Michael
    Pulyakhina, Irina
    Anvar, Seyed Yahya
    Laros, Jeroen F J
    Buermans, Henk P J
    Karlberg, Olof
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular Medicine. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Brännvall, Mathias
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular Medicine. Uppsala University, Science for Life Laboratory, SciLifeLab.
    den Dunnen, Johan T
    van Ommen, Gert-Jan B
    Gut, Ivo G
    Guigó, Roderic
    Estivill, Xavier
    Syvänen, Ann-Christine
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular Medicine. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Dermitzakis, Emmanouil T
    Lappalainen, Tuuli
    Reproducibility of high-throughput mRNA and small RNA sequencing across laboratories2013In: Nature Biotechnology, ISSN 1087-0156, E-ISSN 1546-1696, Vol. 31, no 11, p. 1015-1022Article in journal (Refereed)
    Abstract [en]

    RNA sequencing is an increasingly popular technology for genome-wide analysis of transcript sequence and abundance. However, understanding of the sources of technical and interlaboratory variation is still limited. To address this, the GEUVADIS consortium sequenced mRNAs and small RNAs of lymphoblastoid cell lines of 465 individuals in seven sequencing centers, with a large number of replicates. The variation between laboratories appeared to be considerably smaller than the already limited biological variation. Laboratory effects were mainly seen in differences in insert size and GC content and could be adequately corrected for. In small-RNA sequencing, the microRNA (miRNA) content differed widely between samples owing to competitive sequencing of rRNA fragments. This did not affect relative quantification of miRNAs. We conclude that distributing RNA sequencing among different laboratories is feasible, given proper standardization and randomization procedures. We provide a set of quality measures and guidelines for assessing technical biases in RNA-seq data.

1 - 20 of 20
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