{"entity": "researcher", "timestamp": "2026-08-16T10:51:32.524Z", "family": "Sandling", "given": "Johanna K", "initials": "JK", "orcid": "0000-0003-1382-2321", "affiliations": ["Department of Medical Sciences, Rheumatology, Uppsala University, Uppsala, Sweden johanna.sandling@medsci.uu.se Lars.Ronnblom@medsci.uu.se."], "links": {"self": {"href": "https://publications.scilifelab.se/researcher/9c7bae5a05ac47eeac96547ca7336767.json"}, "display": {"href": "https://publications.scilifelab.se/researcher/9c7bae5a05ac47eeac96547ca7336767"}}, "publications": [{"entity": "publication", "iuid": "62aeb5e95c7f40e5b971a1dd1f521f6e", "links": {"self": {"href": "https://publications.scilifelab.se/publication/62aeb5e95c7f40e5b971a1dd1f521f6e.json"}, "display": {"href": "https://publications.scilifelab.se/publication/62aeb5e95c7f40e5b971a1dd1f521f6e"}}, "title": "Genetic risk factors and clinical manifestations of systemic lupus erythematosus: Large-scale analysis of genetic predisposition and disease subtypes.", "authors": [{"family": "Reid", "given": "Sarah", "initials": "S"}, {"family": "Sandling", "given": "Johanna K", "initials": "JK", "orcid": "0000-0003-1382-2321", "researcher": {"href": "https://publications.scilifelab.se/researcher/9c7bae5a05ac47eeac96547ca7336767.json"}}, {"family": "Pucholt", "given": "Pascal", "initials": "P"}, {"family": "Sayadi", "given": "Ahmed", "initials": "A"}, {"family": "Frodlund", "given": "Martina", "initials": "M"}, {"family": "Lerang", "given": "Karoline", "initials": "K"}, {"family": "Gunnarsson", "given": "Iva", "initials": "I"}, {"family": "J\u00f6nsen", "given": "Andreas", "initials": "A"}, {"family": "Syv\u00e4nen", "given": "Ann-Christine", "initials": "AC"}, {"family": "Molberg", "given": "\u00d8yvind", "initials": "\u00d8"}, {"family": "Rantap\u00e4\u00e4-Dahlqvist", "given": "Solbritt", "initials": "S", "orcid": "0000-0001-8259-3863", "researcher": {"href": "https://publications.scilifelab.se/researcher/dfca4bfdcf3946fda64397d3b7debc59.json"}}, {"family": "Rudin", "given": "Anna", "initials": "A", "orcid": "0000-0002-4137-1276", "researcher": {"href": "https://publications.scilifelab.se/researcher/fa2b87964bc0472b88fa4267ee23c483.json"}}, {"family": "Sj\u00f6wall", "given": "Christopher", "initials": "C", "orcid": "0000-0003-0900-2048", "researcher": {"href": "https://publications.scilifelab.se/researcher/fe4dd47b8ca1436e8a26fdea33f5e7f6.json"}}, {"family": "Svenungsson", "given": "Elisabet", "initials": "E", "orcid": "0000-0003-3396-3244", "researcher": {"href": "https://publications.scilifelab.se/researcher/0ab5989c3c604a96bf42b1b6f90434a0.json"}}, {"family": "Bengtsson", "given": "Anders A", "initials": "AA"}, {"family": "R\u00f6nnblom", "given": "Lars", "initials": "L", "orcid": "0000-0001-9403-6503", "researcher": {"href": "https://publications.scilifelab.se/researcher/053ed3b657124a1bab3a78dc685556e6.json"}}, {"family": "Leonard", "given": "Dag", "initials": "D", "orcid": "0000-0002-6275-7282", "researcher": {"href": "https://publications.scilifelab.se/researcher/42ed25c2f495484db4757f4fef51abae.json"}}], "type": "journal article", "published": "2026-01-00", "journal": {"title": "J. Intern. Med.", "issn": "1365-2796", "volume": "299", "issue": "1", "pages": "95-108", "issn-l": "0954-6820"}, "abstract": "Systemic lupus erythematosus (SLE) is an autoimmune disease with a heterogenous clinical picture. This study aimed to link genetic SLE predisposition with relevant clinical manifestations.\n\nDatasets best corresponding to the 11 American College of Rheumatology 1982 (ACR-82) classification criteria for SLE in a large, public database (FinnGen consortium, >218,000 individuals) were identified. Mendelian randomization analysis was conducted to evaluate the effect of a high genetic SLE predisposition on each manifestation. Next, validation was conducted in a clinical SLE cohort comprising 1487 genotyped Scandinavian patients with detailed clinical data. Based on the public datasets, genetic risk scores (GRSs) for each relevant manifestation were constructed for each patient. Associations between each GRS and the corresponding ACR-82 criterion were evaluated using logistic regression.\n\nIn the FinnGen biobank, the cumulative effect of the 57 SLE risk SNPs was associated with an increased risk of rosacea, OR 1.09 (1.03-1.16), polyarthropathies, OR 1.10 (1.06-1.14), pleural effusions, OR 1.09 (1.04-1.14), and hemolytic anemia, OR 1.32 (1.10-1.58). In the clinical cohort, 5 of the 11 GRSs generated from the public datasets were associated with their corresponding ACR-82 criterion: arthritis, OR 1.15 (1.02-1.31), renal disorder, OR 1.15 (1.04-1.29), neurologic disorder, OR 1.24 (1.04-1.47), hematologic disorder, OR 1.12 (1.00-1.24), and immunologic disorder, OR 1.37 (1.22-1.56).\n\nThe findings demonstrate that known SLE risk gene variants play a role in the development of at least half of the ACR-82 criteria for SLE, indicating a future possibility of using genetics to predict a variety of disease sub-phenotypes in SLE.", "doi": "10.1111/joim.70040", "pmid": "41200769", "labels": {"NGI SNP genotyping": "Service", "NGI Uppsala (SNP&SEQ Technology Platform)": "Service", "National Genomics Infrastructure": "Service"}, "xrefs": [{"db": "pmc", "key": "PMC12678220"}], "notes": [], "created": "2026-06-01T08:45:42.226Z", "modified": "2026-06-01T08:45:42.343Z"}, {"entity": "publication", "iuid": "ab8fa0c345a2433995ebac47f3ad0b58", "links": {"self": {"href": "https://publications.scilifelab.se/publication/ab8fa0c345a2433995ebac47f3ad0b58.json"}, "display": {"href": "https://publications.scilifelab.se/publication/ab8fa0c345a2433995ebac47f3ad0b58"}}, "title": "Rare and common single nucleotide variants in childhood-onset systemic lupus erythematosus.", "authors": [{"family": "Sayadi", "given": "Ahmed", "initials": "A", "orcid": "0000-0002-5662-9145", "researcher": {"href": "https://publications.scilifelab.se/researcher/0f74f301499b4f888e0ac7c5161ae161.json"}}, {"family": "Sandling", "given": "Johanna K", "initials": "JK", "orcid": "0000-0003-1382-2321", "researcher": {"href": "https://publications.scilifelab.se/researcher/9c7bae5a05ac47eeac96547ca7336767.json"}}, {"family": "Eloranta", "given": "Maija-Leena", "initials": "ML", "orcid": "0000-0002-8454-1351", "researcher": {"href": "https://publications.scilifelab.se/researcher/d162e060954d420e825884f254886dcd.json"}}, {"family": "ImmunoArray Development Consortium", "given": "", "initials": ""}, {"family": "DISSECT Consortium", "given": "", "initials": ""}, {"family": "J\u00f6nsen", "given": "Andreas", "initials": "A"}, {"family": "Gunnarsson", "given": "Iva", "initials": "I"}, {"family": "Rantap\u00e4\u00e4-Dahlqvist", "given": "Solbritt", "initials": "S", "orcid": "0000-0001-8259-3863", "researcher": {"href": "https://publications.scilifelab.se/researcher/dfca4bfdcf3946fda64397d3b7debc59.json"}}, {"family": "Sj\u00f6wall", "given": "Christopher", "initials": "C", "orcid": "0000-0003-0900-2048", "researcher": {"href": "https://publications.scilifelab.se/researcher/fe4dd47b8ca1436e8a26fdea33f5e7f6.json"}}, {"family": "Bengtsson", "given": "Anders A", "initials": "AA"}, {"family": "Svenungsson", "given": "Elisabet", "initials": "E", "orcid": "0000-0003-3396-3244", "researcher": {"href": "https://publications.scilifelab.se/researcher/0ab5989c3c604a96bf42b1b6f90434a0.json"}}, {"family": "Lindblad-Toh", "given": "Kerstin", "initials": "K", "orcid": "0000-0001-8338-0253", "researcher": {"href": "https://publications.scilifelab.se/researcher/e0063145f7d6476f80ab42f94833f4cf.json"}}, {"family": "Leonard", "given": "Dag", "initials": "D", "orcid": "0000-0002-6275-7282", "researcher": {"href": "https://publications.scilifelab.se/researcher/42ed25c2f495484db4757f4fef51abae.json"}}, {"family": "R\u00f6nnblom", "given": "Lars", "initials": "L", "orcid": "0000-0001-9403-6503", "researcher": {"href": "https://publications.scilifelab.se/researcher/053ed3b657124a1bab3a78dc685556e6.json"}}, {"family": " DISSECT Consortium", "given": "", "initials": ""}], "type": "journal article", "published": "2025-02-11", "journal": {"title": "Lupus Sci Med", "issn": "2053-8790", "volume": "12", "issue": "1", "issn-l": "2053-8790"}, "abstract": "SLE is a systemic autoimmune disease with a large number of common risk gene variants, but several rare gene variants can cause monogenic SLE. The relationship between common and rare variants in SLE is unclear. We therefore investigated the occurrence of rare deleterious variants in patients with childhood-onset SLE (cSLE) and adult-onset SLE (aSLE) and compared the frequency of these variants with their individual SLE polygenic risk score (PRS).\n\nTargeted sequencing of 1832 gene regions, including coding regions of 31 genes associated with monogenic SLE, was performed in 958 patients with SLE and 1026 healthy individuals. A total of 116 patients with SLE had disease onset before the age of 18 (cSLE). An SLE common variant PRS was created from 37 SLE genome-wide association study single nucleotide variants (SNVs).\n\nRare coding deleterious SNVs (RD SNVs) were observed in 23 of the monogenic SLE-associated genes. Six per cent of patients with cSLE, compared with 3.2% of controls and 4.6% of patients with aSLE, carried rare deleterious alleles. In cSLE, RD SNVs were observed in the C1S, DDX58, IFIH1, IKZF1, RNASEH2A and C8A genes. A PRS analysis showed that patients with cSLE with any of these gene variants had a similar average PRS as control individuals.\n\nRD SNVs were observed in a small proportion of cSLE and carriers of these RD SNVs had a PRS similar to healthy individuals, suggesting the importance of rare coding heterozygous variants in driving disease risk in a subset of children with SLE.", "doi": "10.1136/lupus-2024-001436", "pmid": "39933823", "labels": {"NGI Uppsala (SNP&SEQ Technology Platform)": "Service", "National Genomics Infrastructure": "Service", "NGI Short read": "Service"}, "xrefs": [{"db": "pii", "key": "12/1/e001436"}], "notes": [], "created": "2025-02-12T13:49:33.306Z", "modified": "2025-03-24T08:21:29.400Z"}, {"entity": "publication", "iuid": "9aef338ade194b078421af40a611fa5a", "links": {"self": {"href": "https://publications.scilifelab.se/publication/9aef338ade194b078421af40a611fa5a.json"}, "display": {"href": "https://publications.scilifelab.se/publication/9aef338ade194b078421af40a611fa5a"}}, "title": "B cell polygenic risk scores associate with anti-dsDNA antibodies and nephritis in systemic lupus erythematosus.", "authors": [{"family": "Hedenstedt", "given": "Anna", "initials": "A", "orcid": "0009-0007-1596-1233", "researcher": {"href": "https://publications.scilifelab.se/researcher/83ae75c2cfd64c9488ea2a07119d0f4d.json"}}, {"family": "Reid", "given": "Sarah", "initials": "S"}, {"family": "Sayadi", "given": "Ahmed", "initials": "A"}, {"family": "Eloranta", "given": "Maija-Leena", "initials": "ML", "orcid": "0000-0002-8454-1351", "researcher": {"href": "https://publications.scilifelab.se/researcher/d162e060954d420e825884f254886dcd.json"}}, {"family": "Skoglund", "given": "Elisabeth", "initials": "E"}, {"family": "Bolin", "given": "Karin", "initials": "K"}, {"family": "Frodlund", "given": "Martina", "initials": "M"}, {"family": "Lerang", "given": "Karoline", "initials": "K"}, {"family": "J\u00f6nsen", "given": "Andreas", "initials": "A"}, {"family": "Rantap\u00e4\u00e4-Dahlqvist", "given": "Solbritt", "initials": "S"}, {"family": "Bengtsson", "given": "Anders A", "initials": "AA"}, {"family": "Rudin", "given": "Anna", "initials": "A"}, {"family": "Molberg", "given": "\u00d8yvind", "initials": "\u00d8"}, {"family": "Sj\u00f6wall", "given": "Christopher", "initials": "C", "orcid": "0000-0003-0900-2048", "researcher": {"href": "https://publications.scilifelab.se/researcher/fe4dd47b8ca1436e8a26fdea33f5e7f6.json"}}, {"family": "Sandling", "given": "Johanna K", "initials": "JK", "orcid": "0000-0003-1382-2321", "researcher": {"href": "https://publications.scilifelab.se/researcher/9c7bae5a05ac47eeac96547ca7336767.json"}}, {"family": "Leonard", "given": "Dag", "initials": "D", "orcid": "0000-0002-6275-7282", "researcher": {"href": "https://publications.scilifelab.se/researcher/42ed25c2f495484db4757f4fef51abae.json"}}], "type": "journal article", "published": "2023-10-00", "journal": {"title": "Lupus Sci Med", "issn": "2053-8790", "volume": "10", "issue": "2", "issn-l": "2053-8790"}, "abstract": "B cell function and autoantibodies are important in SLE pathogenesis. In this work, we aimed to investigate the impact of cumulative SLE B cell genetics on SLE subphenotype and autoantibody profile.\n\nFemale patients with SLE (n=1248) and healthy controls (n=400) were genotyped using Illumina's Global Screening Array. Two polygenic risk scores (PRSs), one representing B cell genes and the other B cell activation genes, were calculated for each individual using risk loci for SLE in genes assigned to B cell-related pathways according to the Kyoto Encyclopedia of Genes and Genomes, Gene Ontology and Reactome Databases.\n\nDouble-stranded DNA (dsDNA) antibodies were more prevalent among patients with a high compared with a low SLE B cell PRS (OR 1.47 (1.07 to 2.01), p=0.018), and effect sizes were augmented in patients with human leucocyte antigen (HLA) risk haplotypes HLA-DRB1*03:01 and HLA-DRB1*15:01 (DRB1*03/15 -/- (OR 0.99 (0.56 to 1.77), p=0.98; DRB1*03/15 +/- or -/+ (OR 1.64 (1.06 to 2.54), p=0.028; and DRB1*03/15 +/+ (OR 4.47 (1.21 to 16.47), p=0.024). Further, a high compared with a low B cell PRS was associated with low complement levels in DRB1*03/15 +/+ patients (OR 3.92 (1.22 to 12.64), p=0.022). The prevalence of lupus nephritis (LN) was higher in patients with a B cell activation PRS above the third quartile compared with patients below (OR 1.32 (1.00 to 1.74), p=0.048).\n\nHigh genetic burden related to B cell function is associated with dsDNA antibody development and LN. Assessing B cell PRSs may be important in order to determine immunological pathways influencing SLE and to predict clinical phenotype.", "doi": "10.1136/lupus-2023-000926", "pmid": "37844960", "labels": {"NGI Short read": "Service", "NGI SNP genotyping": "Service", "NGI Uppsala (SNP&SEQ Technology Platform)": "Service", "National Genomics Infrastructure": "Service"}, "xrefs": [{"db": "pmc", "key": "PMC10582984"}, {"db": "pii", "key": "10/2/e000926"}], "notes": [], "created": "2023-11-29T10:59:36.253Z", "modified": "2023-11-29T10:59:36.317Z"}, {"entity": "publication", "iuid": "12159c4661c1445a9deed2ed84fce70f", "links": {"self": {"href": "https://publications.scilifelab.se/publication/12159c4661c1445a9deed2ed84fce70f.json"}, "display": {"href": "https://publications.scilifelab.se/publication/12159c4661c1445a9deed2ed84fce70f"}}, "title": "Mer-tyrosine kinase: a novel susceptibility gene for SLE related end-stage renal disease.", "authors": [{"family": "Yavuz", "given": "Sule", "initials": "S"}, {"family": "Pucholt", "given": "Pascal", "initials": "P", "orcid": "0000-0003-3342-1373", "researcher": {"href": "https://publications.scilifelab.se/researcher/61a214ff2d494b568cb6da944e858acf.json"}}, {"family": "Sandling", "given": "Johanna K", "initials": "JK", "orcid": "0000-0003-1382-2321", "researcher": {"href": "https://publications.scilifelab.se/researcher/9c7bae5a05ac47eeac96547ca7336767.json"}}, {"family": "Bianchi", "given": "Matteo", "initials": "M"}, {"family": "Leonard", "given": "Dag", "initials": "D", "orcid": "0000-0002-6275-7282", "researcher": {"href": "https://publications.scilifelab.se/researcher/42ed25c2f495484db4757f4fef51abae.json"}}, {"family": "Bolin", "given": "Karin", "initials": "K"}, {"family": "Imgenberg-Kreuz", "given": "Juliana", "initials": "J"}, {"family": "Eloranta", "given": "Maija-Leena", "initials": "ML"}, {"family": "Kozyrev", "given": "Sergey V", "initials": "SV", "orcid": "0000-0001-6209-4100", "researcher": {"href": "https://publications.scilifelab.se/researcher/b6be89ad73a14d66a3b9439efc9c4099.json"}}, {"family": "Lanata", "given": "Cristina M", "initials": "CM"}, {"family": "J\u00f6nsen", "given": "Andreas", "initials": "A"}, {"family": "Bengtsson", "given": "Anders A", "initials": "AA"}, {"family": "Sj\u00f6wall", "given": "Christopher", "initials": "C", "orcid": "0000-0003-0900-2048", "researcher": {"href": "https://publications.scilifelab.se/researcher/fe4dd47b8ca1436e8a26fdea33f5e7f6.json"}}, {"family": "Svenungsson", "given": "Elisabet", "initials": "E", "orcid": "0000-0003-3396-3244", "researcher": {"href": "https://publications.scilifelab.se/researcher/0ab5989c3c604a96bf42b1b6f90434a0.json"}}, {"family": "Gunnarsson", "given": "Iva", "initials": "I"}, {"family": "Rantap\u00e4\u00e4-Dahlqvist", "given": "Solbritt", "initials": "S"}, {"family": "ImmunoArray Development Consortium", "given": "", "initials": ""}, {"family": "DISSECT Consortium", "given": "", "initials": ""}, {"family": "Nititham", "given": "Joanne", "initials": "J"}, {"family": "Criswell", "given": "Lindsey A", "initials": "LA"}, {"family": "Lindblad-Toh", "given": "Kerstin", "initials": "K"}, {"family": "R\u00f6nnblom", "given": "Lars", "initials": "L", "orcid": "0000-0001-9403-6503", "researcher": {"href": "https://publications.scilifelab.se/researcher/053ed3b657124a1bab3a78dc685556e6.json"}}], "type": "meta-analysis", "published": "2022-11-00", "journal": {"title": "Lupus Sci Med", "issn": "2053-8790", "volume": "9", "issue": "1", "issn-l": "2053-8790"}, "abstract": "Lupus nephritis (LN) is a common and severe manifestation of SLE. The genetic risk for nephritis and progression to end-stage renal disease (ESRD) in patients with LN remains unclear. Herein, we aimed to identify novel genetic associations with LN, focusing on subphenotypes and ESRD.\n\nWe analysed genomic data on 958 patients with SLE (discovery cohort: LN=338) with targeted sequencing data from 1832 immunological pathway genes. We used an independent multiethnic cohort comprising 1226 patients with SLE (LN=603) as a replication dataset. Detailed functional annotation and functional epigenomic enrichment analyses were applied to predict functional effects of the candidate variants.\n\nA genetic variant (rs56097910) within the MERTK gene was associated with ESRD in both cohorts, meta-analysis OR=5.4 (2.8 to 10.6); p=1.0\u00d710-6. We observed decreased methylation levels in peripheral blood cells from SLE patients with ESRD, compared with patients without renal SLE (p=2.7\u00d710-4), at one CpG site (cg16333401) in close vicinity to the transcription start site of MERTK and located in a DNAse hypersensitivity region in T and B cells. Rs56097910 is linked to altered MERTK expression in kidney tissue in public eQTL databases. Two loci were replicated for association with proliferative LN: PRDM1 (rs6924535, pmeta=1.6\u00d710-5, OR=0.58) and APOA1BP (NAXE) (rs942960, pmeta=1.2\u00d710-5, OR=2.64).\n\nWe identified a novel genetic risk locus, MERTK, associated with SLE-ESRD using the data from two large SLE cohorts. Through DNA methylation analysis and functional annotation, we showed that the risk could be mediated through regulation of gene expression. Our results suggest that variants in the MERTK gene are important for the risk of developing SLE-ESRD and suggest a role for PRDM1 and APOA1BP in proliferative LN.", "doi": "10.1136/lupus-2022-000752", "pmid": "36332927", "labels": {"NGI Short read": "Service", "NGI SNP genotyping": "Service", "NGI Uppsala (SNP&SEQ Technology Platform)": "Service", "National Genomics Infrastructure": "Service", "Bioinformatics Support for Computational Resources": "Service"}, "xrefs": [{"db": "pmc", "key": "PMC9639142"}, {"db": "pii", "key": "9/1/e000752"}], "notes": [], "created": "2022-11-29T12:21:01.345Z", "modified": "2024-01-16T13:48:34.678Z"}, {"entity": "publication", "iuid": "28bea3b7207d47f79712b969b987d91b", "links": {"self": {"href": "https://publications.scilifelab.se/publication/28bea3b7207d47f79712b969b987d91b.json"}, "display": {"href": "https://publications.scilifelab.se/publication/28bea3b7207d47f79712b969b987d91b"}}, "title": "Contribution of Rare Genetic Variation to Disease Susceptibility in a Large Scandinavian Myositis Cohort.", "authors": [{"family": "Bianchi", "given": "Matteo", "initials": "M", "orcid": "0000-0003-3394-6495", "researcher": {"href": "https://publications.scilifelab.se/researcher/d645ef0e04a245f0ac9e7d7498b2bd69.json"}}, {"family": "Kozyrev", "given": "Sergey V", "initials": "SV", "orcid": "0000-0001-6209-4100", "researcher": {"href": "https://publications.scilifelab.se/researcher/b6be89ad73a14d66a3b9439efc9c4099.json"}}, {"family": "Notarnicola", "given": "Antonella", "initials": "A", "orcid": "0000-0003-0272-2931", "researcher": {"href": "https://publications.scilifelab.se/researcher/42411ecc60cd4357930ff0e978b3fcd8.json"}}, {"family": "Hultin Rosenberg", "given": "Lina", "initials": "L"}, {"family": "Karlsson", "given": "\u00c5sa", "initials": "\u00c5"}, {"family": "Pucholt", "given": "Pascal", "initials": "P", "orcid": "0000-0003-3342-1373", "researcher": {"href": "https://publications.scilifelab.se/researcher/61a214ff2d494b568cb6da944e858acf.json"}}, {"family": "Rothwell", "given": "Simon", "initials": "S", "orcid": "0000-0003-2123-9902", "researcher": {"href": "https://publications.scilifelab.se/researcher/b39ce853a3d041b68e4d4e82e64e3703.json"}}, {"family": "Alexsson", "given": "Andrei", "initials": "A"}, {"family": "Sandling", "given": "Johanna K", "initials": "JK", "orcid": "0000-0003-1382-2321", "researcher": {"href": "https://publications.scilifelab.se/researcher/9c7bae5a05ac47eeac96547ca7336767.json"}}, {"family": "Andersson", "given": "Helena", "initials": "H"}, {"family": "Cooper", "given": "Robert G", "initials": "RG"}, {"family": "Padyukov", "given": "Leonid", "initials": "L", "orcid": "0000-0003-2950-5670", "researcher": {"href": "https://publications.scilifelab.se/researcher/052dbef663f442f2a72161d634b9ce7d.json"}}, {"family": "Tj\u00e4rnlund", "given": "Anna", "initials": "A"}, {"family": "Dastmalchi", "given": "Maryam", "initials": "M"}, {"family": "ImmunoArray Development Consortium", "given": "", "initials": ""}, {"family": "DISSECT Consortium", "given": "", "initials": ""}, {"family": "Meadows", "given": "Jennifer R S", "initials": "JRS", "orcid": "0000-0002-0850-230X", "researcher": {"href": "https://publications.scilifelab.se/researcher/86acdca0104c4552880d5a7cb5ac6565.json"}}, {"family": "Pyndt Diederichsen", "given": "Louise", "initials": "L"}, {"family": "Molberg", "given": "\u00d8yvind", "initials": "\u00d8"}, {"family": "Chinoy", "given": "Hector", "initials": "H", "orcid": "0000-0001-6492-1288", "researcher": {"href": "https://publications.scilifelab.se/researcher/03b0a1d459104296baba3dedebf10e08.json"}}, {"family": "Lamb", "given": "Janine A", "initials": "JA", "orcid": "0000-0002-7248-0539", "researcher": {"href": "https://publications.scilifelab.se/researcher/290c4b3570124cbea63a99516c294da2.json"}}, {"family": "R\u00f6nnblom", "given": "Lars", "initials": "L", "orcid": "0000-0001-9403-6503", "researcher": {"href": "https://publications.scilifelab.se/researcher/053ed3b657124a1bab3a78dc685556e6.json"}}, {"family": "Lindblad-Toh", "given": "Kerstin", "initials": "K", "orcid": "0000-0001-8338-0253", "researcher": {"href": "https://publications.scilifelab.se/researcher/e0063145f7d6476f80ab42f94833f4cf.json"}}, {"family": "Lundberg", "given": "Ingrid E", "initials": "IE", "orcid": "0000-0002-6068-9212", "researcher": {"href": "https://publications.scilifelab.se/researcher/40f6c8e761a944b78e67f0e04453f78b.json"}}], "type": "journal article", "published": "2022-02-00", "journal": {"title": "Arthritis & rheumatology (Hoboken, N.J.)", "issn": "2326-5205", "volume": "74", "issue": "2", "pages": "342-352", "issn-l": "2326-5191"}, "abstract": "Idiopathic inflammatory myopathies (IIMs) are a heterogeneous group of complex autoimmune conditions characterized by inflammation in skeletal muscle and extramuscular compartments, and interferon (IFN) system activation. We undertook this study to examine the contribution of genetic variation to disease susceptibility and to identify novel avenues for research in IIMs.\n\nTargeted DNA sequencing was used to mine coding and potentially regulatory single nucleotide variants from ~1,900 immune-related genes in a Scandinavian case-control cohort of 454 IIM patients and 1,024 healthy controls. Gene-based aggregate testing, together with rare variant- and gene-level enrichment analyses, was implemented to explore genotype-phenotype relations.\n\nGene-based aggregate tests of all variants, including rare variants, identified IFI35 as a potential genetic risk locus for IIMs, suggesting a genetic signature of type I IFN pathway activation. Functional annotation of the IFI35 locus highlighted a regulatory network linked to the skeletal muscle-specific gene PTGES3L, as a potential candidate for IIM pathogenesis. Aggregate genetic associations with AGER and PSMB8 in the major histocompatibility complex locus were detected in the antisynthetase syndrome subgroup, which also showed a less marked genetic signature of the type I IFN pathway. Enrichment analyses indicated a burden of synonymous and noncoding rare variants in IIM patients, suggesting increased disease predisposition associated with these classes of rare variants.\n\nOur study suggests the contribution of rare genetic variation to disease susceptibility in IIM and specific patient subgroups, and pinpoints genetic associations consistent with previous findings by gene expression profiling. These features highlight genetic profiles that are potentially relevant to disease pathogenesis.", "doi": "10.1002/art.41929", "pmid": "34279065", "labels": {"Bioinformatics Support for Computational Resources": "Service"}, "xrefs": [], "notes": [], "created": "2023-11-27T21:41:26.094Z", "modified": "2024-01-16T13:48:37.654Z"}, {"entity": "publication", "iuid": "9e5836ea464143e5ba4a0f2b0cc29cb3", "links": {"self": {"href": "https://publications.scilifelab.se/publication/9e5836ea464143e5ba4a0f2b0cc29cb3.json"}, "display": {"href": "https://publications.scilifelab.se/publication/9e5836ea464143e5ba4a0f2b0cc29cb3"}}, "title": "Interaction between the STAT4 rs11889341(T) risk allele and smoking confers increased risk of myocardial infarction and nephritis in patients with systemic lupus erythematosus.", "authors": [{"family": "Reid", "given": "Sarah", "initials": "S", "orcid": "0000-0003-4065-6875", "researcher": {"href": "https://publications.scilifelab.se/researcher/689ab046bc19433483d502284d2c51c4.json"}}, {"family": "Hagberg", "given": "Niklas", "initials": "N", "orcid": "0000-0003-2064-2716", "researcher": {"href": "https://publications.scilifelab.se/researcher/0d0998bb419c424083b0978ebdbe8629.json"}}, {"family": "Sandling", "given": "Johanna K", "initials": "JK", "orcid": "0000-0003-1382-2321", "researcher": {"href": "https://publications.scilifelab.se/researcher/9c7bae5a05ac47eeac96547ca7336767.json"}}, {"family": "Alexsson", "given": "Andrei", "initials": "A"}, {"family": "Pucholt", "given": "Pascal", "initials": "P", "orcid": "0000-0003-3342-1373", "researcher": {"href": "https://publications.scilifelab.se/researcher/61a214ff2d494b568cb6da944e858acf.json"}}, {"family": "Sj\u00f6wall", "given": "Christopher", "initials": "C", "orcid": "0000-0003-0900-2048", "researcher": {"href": "https://publications.scilifelab.se/researcher/fe4dd47b8ca1436e8a26fdea33f5e7f6.json"}}, {"family": "Lerang", "given": "Karoline", "initials": "K"}, {"family": "J\u00f6nsen", "given": "Andreas", "initials": "A"}, {"family": "Gunnarsson", "given": "Iva", "initials": "I"}, {"family": "Syv\u00e4nen", "given": "Ann-Christine", "initials": "AC"}, {"family": "Troldborg", "given": "Anne Margrethe", "initials": "AM"}, {"family": "Voss", "given": "Anne", "initials": "A"}, {"family": "Bengtsson", "given": "Anders A", "initials": "AA"}, {"family": "Molberg", "given": "\u00d8yvind", "initials": "\u00d8"}, {"family": "Jacobsen", "given": "S\u00f8ren", "initials": "S"}, {"family": "Svenungsson", "given": "Elisabet", "initials": "E", "orcid": "0000-0003-3396-3244", "researcher": {"href": "https://publications.scilifelab.se/researcher/0ab5989c3c604a96bf42b1b6f90434a0.json"}}, {"family": "R\u00f6nnblom", "given": "Lars", "initials": "L", "orcid": "0000-0001-9403-6503", "researcher": {"href": "https://publications.scilifelab.se/researcher/053ed3b657124a1bab3a78dc685556e6.json"}}, {"family": "Leonard", "given": "Dag", "initials": "D"}], "type": "journal article", "published": "2021-09-00", "journal": {"title": "Ann. Rheum. Dis.", "issn": "1468-2060", "issn-l": "0003-4967", "volume": "80", "issue": "9", "pages": "1183-1189"}, "abstract": "To investigate how genetics influence the risk of smoking-related systemic lupus erythematosus (SLE) manifestations.\n\nPatients with SLE (ndiscovery cohort=776, nreplication cohort=836) were genotyped using the 200K Immunochip single nucleotide polymorphisms (SNP) Array (Illumina) and a custom array. Sixty SNPs with SLE association (p<5.0\u00d710-8) were analysed. Signal transducer and activator of transcription 4 (STAT4) activation was assessed in in vitro stimulated peripheral blood mononuclear cells from healthy controls (n=45).\n\nIn the discovery cohort, smoking was associated with myocardial infarction (MI) (OR 1.96 (95% CI 1.09 to 3.55)), with a greater effect in patients carrying any rs11889341 STAT4 risk allele (OR 2.72 (95% CI 1.24 to 6.00)) or two risk alleles (OR 8.27 (95% CI 1.48 to 46.27)).Smokers carrying the risk allele also displayed an increased risk of nephritis (OR 1.47 (95% CI 1.06 to 2.03)). In the replication cohort, the high risk of MI in smokers carrying the risk allele and the association between the STAT4 risk allele and nephritis in smokers were confirmed (OR 6.19 (95% CI 1.29 to 29.79) and 1.84 (95% CI 1.05 to 3.29), respectively).The interaction between smoking and the STAT4 risk allele resulted in further increase in the risk of MI (OR 2.14 (95% CI 1.01 to 4.62)) and nephritis (OR 1.53 (95% CI 1.08 to 2.17)), with 54% (MI) and 34% (nephritis) of the risk attributable to the interaction. Levels of interleukin-12-induced phosphorylation of STAT4 in CD8+ T cells were higher in smokers than in non-smokers (mean geometric fluorescence intensity 1063 vs 565, p=0.0063).Lastly, the IL12A rs564799 risk allele displayed association with MI in both cohorts (OR 1.53 (95% CI 1.01 to 2.31) and 2.15 (95% CI 1.08 to 4.26), respectively).\n\nSmoking in the presence of the STAT4 risk gene variant appears to increase the risk of MI and nephritis in SLE. Our results also highlight the role of the IL12-STAT4 pathway in SLE-cardiovascular morbidity.", "doi": "10.1136/annrheumdis-2020-219727", "pmid": "33766895", "labels": {"National Genomics Infrastructure": "Service", "NGI Uppsala (SNP&SEQ Technology Platform)": "Service", "Bioinformatics Support for Computational Resources": "Service"}, "xrefs": [{"db": "pii", "key": "annrheumdis-2020-219727"}, {"db": "pmc", "key": "PMC8372395"}], "notes": [], "created": "2021-04-08T14:44:05.247Z", "modified": "2024-01-16T13:48:38.594Z"}, {"entity": "publication", "iuid": "6c96a8f8b09a4910a4aca433f982ec52", "links": {"self": {"href": "https://publications.scilifelab.se/publication/6c96a8f8b09a4910a4aca433f982ec52.json"}, "display": {"href": "https://publications.scilifelab.se/publication/6c96a8f8b09a4910a4aca433f982ec52"}}, "title": "Molecular pathways in patients with systemic lupus erythematosus revealed by gene-centred DNA sequencing.", "authors": [{"family": "Sandling", "given": "Johanna K", "initials": "JK", "orcid": "0000-0003-1382-2321", "researcher": {"href": "https://publications.scilifelab.se/researcher/9c7bae5a05ac47eeac96547ca7336767.json"}}, {"family": "Pucholt", "given": "Pascal", "initials": "P", "orcid": "0000-0003-3342-1373", "researcher": {"href": "https://publications.scilifelab.se/researcher/61a214ff2d494b568cb6da944e858acf.json"}}, {"family": "Hultin Rosenberg", "given": "Lina", "initials": "L"}, {"family": "Farias", "given": "Fabiana H G", "initials": "FHG"}, {"family": "Kozyrev", "given": "Sergey V", "initials": "SV"}, {"family": "Eloranta", "given": "Maija-Leena", "initials": "ML"}, {"family": "Alexsson", "given": "Andrei", "initials": "A"}, {"family": "Bianchi", "given": "Matteo", "initials": "M"}, {"family": "Padyukov", "given": "Leonid", "initials": "L"}, {"family": "Bengtsson", "given": "Christine", "initials": "C"}, {"family": "Jonsson", "given": "Roland", "initials": "R"}, {"family": "Omdal", "given": "Roald", "initials": "R"}, {"family": "Lie", "given": "Benedicte A", "initials": "BA"}, {"family": "Massarenti", "given": "Laura", "initials": "L"}, {"family": "Steffensen", "given": "Rudi", "initials": "R"}, {"family": "Jakobsen", "given": "Marianne A", "initials": "MA"}, {"family": "Lillevang", "given": "S\u00f8ren T", "initials": "ST"}, {"family": "ImmunoArray Development Consortium and DISSECT consortium", "given": "", "initials": ""}, {"family": "Lerang", "given": "Karoline", "initials": "K"}, {"family": "Molberg", "given": "\u00d8yvind", "initials": "\u00d8"}, {"family": "Voss", "given": "Anne", "initials": "A"}, {"family": "Troldborg", "given": "Anne", "initials": "A"}, {"family": "Jacobsen", "given": "S\u00f8ren", "initials": "S"}, {"family": "Syv\u00e4nen", "given": "Ann-Christine", "initials": "AC"}, {"family": "J\u00f6nsen", "given": "Andreas", "initials": "A"}, {"family": "Gunnarsson", "given": "Iva", "initials": "I"}, {"family": "Svenungsson", "given": "Elisabet", "initials": "E", "orcid": "0000-0003-3396-3244", "researcher": {"href": "https://publications.scilifelab.se/researcher/0ab5989c3c604a96bf42b1b6f90434a0.json"}}, {"family": "Rantap\u00e4\u00e4-Dahlqvist", "given": "Solbritt", "initials": "S"}, {"family": "Bengtsson", "given": "Anders A", "initials": "AA"}, {"family": "Sj\u00f6wall", "given": "Christopher", "initials": "C", "orcid": "0000-0003-0900-2048", "researcher": {"href": "https://publications.scilifelab.se/researcher/fe4dd47b8ca1436e8a26fdea33f5e7f6.json"}}, {"family": "Leonard", "given": "Dag", "initials": "D"}, {"family": "Lindblad-Toh", "given": "Kerstin", "initials": "K", "orcid": "0000-0001-8338-0253", "researcher": {"href": "https://publications.scilifelab.se/researcher/e0063145f7d6476f80ab42f94833f4cf.json"}}, {"family": "R\u00f6nnblom", "given": "Lars", "initials": "L", "orcid": "0000-0001-9403-6503", "researcher": {"href": "https://publications.scilifelab.se/researcher/053ed3b657124a1bab3a78dc685556e6.json"}}], "type": "journal article", "published": "2021-01-00", "journal": {"title": "Ann. Rheum. Dis.", "issn": "1468-2060", "issn-l": "0003-4967", "volume": "80", "issue": "1", "pages": "109-117"}, "abstract": "Systemic lupus erythematosus (SLE) is an autoimmune disease with extensive heterogeneity in disease presentation between patients, which is likely due to an underlying molecular diversity. Here, we aimed at elucidating the genetic aetiology of SLE from the immunity pathway level to the single variant level, and stratify patients with SLE into distinguishable molecular subgroups, which could inform treatment choices in SLE.\n\nWe undertook a pathway-centred approach, using sequencing of immunological pathway genes. Altogether 1832 candidate genes were analysed in 958 Swedish patients with SLE and 1026 healthy individuals. Aggregate and single variant association testing was performed, and we generated pathway polygenic risk scores (PRS).\n\nWe identified two main independent pathways involved in SLE susceptibility: T lymphocyte differentiation and innate immunity, characterised by HLA and interferon, respectively. Pathway PRS defined pathways in individual patients, who on average were positive for seven pathways. We found that SLE organ damage was more pronounced in patients positive for the T or B cell receptor signalling pathways. Further, pathway PRS-based clustering allowed stratification of patients into four groups with different risk score profiles. Studying sets of genes with priors for involvement in SLE, we observed an aggregate common variant contribution to SLE at genes previously reported for monogenic SLE as well as at interferonopathy genes.\n\nOur results show that pathway risk scores have the potential to stratify patients with SLE beyond clinical manifestations into molecular subsets, which may have implications for clinical follow-up and therapy selection.", "doi": "10.1136/annrheumdis-2020-218636", "pmid": "33037003", "labels": {"National Genomics Infrastructure": "Collaborative", "NGI Uppsala (SNP&SEQ Technology Platform)": "Collaborative", "Bioinformatics Support for Computational Resources": "Service"}, "xrefs": [{"db": "pmc", "key": "PMC7788061"}, {"db": "pii", "key": "annrheumdis-2020-218636"}], "notes": [], "created": "2020-12-08T23:53:14.678Z", "modified": "2024-01-16T13:48:41.009Z"}, {"entity": "publication", "iuid": "7a14c5167e074030981441eb5dcefaad", "links": {"self": {"href": "https://publications.scilifelab.se/publication/7a14c5167e074030981441eb5dcefaad.json"}, "display": {"href": "https://publications.scilifelab.se/publication/7a14c5167e074030981441eb5dcefaad"}}, "title": "Function of multiple sclerosis-protective HLA class I alleles revealed by genome-wide protein-quantitative trait loci mapping of interferon signalling.", "authors": [{"family": "Lundtoft", "given": "Christian", "initials": "C", "orcid": "0000-0001-5872-4253", "researcher": {"href": "https://publications.scilifelab.se/researcher/4a05532d3aad4e2dbe00a4724e8dddd8.json"}}, {"family": "Pucholt", "given": "Pascal", "initials": "P", "orcid": "0000-0003-3342-1373", "researcher": {"href": "https://publications.scilifelab.se/researcher/61a214ff2d494b568cb6da944e858acf.json"}}, {"family": "Imgenberg-Kreuz", "given": "Juliana", "initials": "J", "orcid": "0000-0002-7230-8990", "researcher": {"href": "https://publications.scilifelab.se/researcher/5d4c2f630d484ee780c2c12aaabdb939.json"}}, {"family": "Carlsson-Alml\u00f6f", "given": "Jonas", "initials": "J", "orcid": "0000-0002-1211-9821", "researcher": {"href": "https://publications.scilifelab.se/researcher/046904cd12eb4764bd2dcadc876f65d7.json"}}, {"family": "Eloranta", "given": "Maija-Leena", "initials": "ML", "orcid": "0000-0002-8454-1351", "researcher": {"href": "https://publications.scilifelab.se/researcher/d162e060954d420e825884f254886dcd.json"}}, {"family": "Syv\u00e4nen", "given": "Ann-Christine", "initials": "AC", "orcid": "0000-0002-9681-9146", "researcher": {"href": "https://publications.scilifelab.se/researcher/f7012e35025543379380cb90efd71243.json"}}, {"family": "Nordmark", "given": "Gunnel", "initials": "G", "orcid": "0000-0002-3829-7431", "researcher": {"href": "https://publications.scilifelab.se/researcher/188fda53498740dbb007441cc94bb1ad.json"}}, {"family": "Sandling", "given": "Johanna K", "initials": "JK", "orcid": "0000-0003-1382-2321", "researcher": {"href": "https://publications.scilifelab.se/researcher/9c7bae5a05ac47eeac96547ca7336767.json"}}, {"family": "Kockum", "given": "Ingrid", "initials": "I", "orcid": "0000-0002-0867-4726", "researcher": {"href": "https://publications.scilifelab.se/researcher/03ebcc6a01ef4d0db4e4673aff8de5d8.json"}}, {"family": "Olsson", "given": "Tomas", "initials": "T", "orcid": "0000-0002-2938-1877", "researcher": {"href": "https://publications.scilifelab.se/researcher/fd9a20a941214f97a22f010df37cd8e1.json"}}, {"family": "R\u00f6nnblom", "given": "Lars", "initials": "L", "orcid": "0000-0001-9403-6503", "researcher": {"href": "https://publications.scilifelab.se/researcher/053ed3b657124a1bab3a78dc685556e6.json"}}, {"family": "Hagberg", "given": "Niklas", "initials": "N", "orcid": "0000-0003-2064-2716", "researcher": {"href": "https://publications.scilifelab.se/researcher/0d0998bb419c424083b0978ebdbe8629.json"}}], "type": "journal article", "published": "2020-10-00", "journal": {"title": "PLoS Genet.", "issn": "1553-7404", "volume": "16", "issue": "10", "pages": "e1009199", "issn-l": "1553-7390"}, "abstract": "Interferons (IFNs) are cytokines that are central to the host defence against viruses and other microorganisms. If not properly regulated, IFNs may contribute to the pathogenesis of inflammatory autoimmune, or infectious diseases. To identify genetic polymorphisms regulating the IFN system we performed an unbiased genome-wide protein-quantitative trait loci (pQTL) mapping of cell-type specific type I and type II IFN receptor levels and their responses in immune cells from 303 healthy individuals. Seven genome-wide significant (p < 5.0E-8) pQTLs were identified. Two independent SNPs that tagged the multiple sclerosis (MS)-protective HLA class I alleles A*02/A*68 and B*44, respectively, were associated with increased levels of IFNAR2 in B and T cells, with the most prominent effect in IgD-CD27+ memory B cells. The increased IFNAR2 levels in B cells were replicated in cells from an independent set of healthy individuals and in MS patients. Despite increased IFNAR2 levels, B and T cells carrying the MS-protective alleles displayed a reduced response to type I IFN stimulation. Expression and methylation-QTL analysis demonstrated increased mRNA expression of the pseudogene HLA-J in B cells carrying the MS-protective class I alleles, possibly driven via methylation-dependent transcriptional regulation. Together these data suggest that the MS-protective effects of HLA class I alleles are unrelated to their antigen-presenting function, and propose a previously unappreciated function of type I IFN signalling in B and T cells in MS immune-pathogenesis.", "doi": "10.1371/journal.pgen.1009199", "pmid": "33104735", "labels": {"National Genomics Infrastructure": "Service", "NGI Uppsala (SNP&SEQ Technology Platform)": "Service", "Bioinformatics Support for Computational Resources": "Service"}, "xrefs": [{"db": "pii", "key": "PGENETICS-D-20-01001"}, {"db": "pmc", "key": "PMC7644105"}], "notes": [], "created": "2020-11-05T14:07:48.822Z", "modified": "2024-01-16T13:48:41.667Z"}, {"entity": "publication", "iuid": "6c604e82b0474bec8f83ce513a50bfc1", "links": {"self": {"href": "https://publications.scilifelab.se/publication/6c604e82b0474bec8f83ce513a50bfc1.json"}, "display": {"href": "https://publications.scilifelab.se/publication/6c604e82b0474bec8f83ce513a50bfc1"}}, "title": "Toll-like receptors revisited; a possible role for TLR1 in lupus nephritis.", "authors": [{"family": "Yavuz", "given": "Sule", "initials": "S", "orcid": "0000-0001-5053-6426", "researcher": {"href": "https://publications.scilifelab.se/researcher/21855da83e524b939d9e7aec390e49fc.json"}}, {"family": "Bianchi", "given": "Matteo", "initials": "M"}, {"family": "Kozyrev", "given": "Sergey", "initials": "S"}, {"family": "Bolin", "given": "Karin", "initials": "K"}, {"family": "Leonard", "given": "Dag", "initials": "D"}, {"family": "Pucholt", "given": "Pascal", "initials": "P"}, {"family": "Sandling", "given": "Johanna K", "initials": "JK", "orcid": "0000-0003-1382-2321", "researcher": {"href": "https://publications.scilifelab.se/researcher/9c7bae5a05ac47eeac96547ca7336767.json"}}, {"family": "Bengtsson", "given": "Anders", "initials": "A"}, {"family": "J\u00f6nsen", "given": "Andreas", "initials": "A"}, {"family": "Rantap\u00e4\u00e4-Dahlqvist", "given": "Solbritt", "initials": "S"}, {"family": "Sj\u00f6wall", "given": "Christopher", "initials": "C", "orcid": "0000-0003-0900-2048", "researcher": {"href": "https://publications.scilifelab.se/researcher/fe4dd47b8ca1436e8a26fdea33f5e7f6.json"}}, {"family": "Svenungsson", "given": "Elisabet", "initials": "E", "orcid": "0000-0003-3396-3244", "researcher": {"href": "https://publications.scilifelab.se/researcher/0ab5989c3c604a96bf42b1b6f90434a0.json"}}, {"family": "Gunnarsson", "given": "Iva", "initials": "I"}, {"family": "Lindblad-Toh", "given": "Kerstin", "initials": "K", "orcid": "0000-0001-8338-0253", "researcher": {"href": "https://publications.scilifelab.se/researcher/e0063145f7d6476f80ab42f94833f4cf.json"}}, {"family": "R\u00f6nnblom", "given": "Lars", "initials": "L"}], "type": "letter", "published": "2020-09-29", "journal": {"title": "Ann. Rheum. Dis.", "issn": "1468-2060", "volume": "80", "issue": "3", "pages": "404-406", "issn-l": "0003-4967"}, "abstract": null, "doi": "10.1136/annrheumdis-2020-218373", "pmid": "32994161", "labels": {"National Genomics Infrastructure": "Service", "NGI Uppsala (SNP&SEQ Technology Platform)": "Service"}, "xrefs": [{"db": "pii", "key": "annrheumdis-2020-218373"}, {"db": "pmc", "key": "PMC7892377"}], "notes": [], "created": "2020-12-08T23:29:04.091Z", "modified": "2021-11-10T12:46:58.369Z"}]}