Teruel, MaríaBarturen, GuillermoMartínez-Bueno, ManuelCastellini-Pérez, OliviaBarroso-Gil, MiguelPovedano, ElenaKerick, MartinCatalà-Moll, FrancescMakowska, ZuzannaButtgereit, AnnePers, Jacques-OlivierMarañón, ConcepciónBallestar, EstebanMartin, JavierCarnero-Montoro, ElenaAlarcón-Riquelme, Marta E.2023-01-102023-01-102021-12-02Teruel M, Barturen G, Martínez-Bueno M, Castellini-Pérez O, Barroso-Gil M, Povedano E, Kerick M, et al. Integrative epigenomics in Sjögren´s syndrome reveals novel pathways and a strong interaction between the HLA, autoantibodies and the interferon signature. Sci Rep. 2021 Dec 2;11(1):23292http://hdl.handle.net/10668/4558Primary Sjögren’s syndrome (SS) is a systemic autoimmune disease characterized by lymphocytic infiltration and damage of exocrine salivary and lacrimal glands. The etiology of SS is complex with environmental triggers and genetic factors involved. By conducting an integrated multi-omics study, we confirmed a vast coordinated hypomethylation and overexpression effects in IFN-related genes, what is known as the IFN signature. Stratified and conditional analyses suggest a strong interaction between SS-associated HLA genetic variation and the presence of Anti-Ro/SSA autoantibodies in driving the IFN epigenetic signature and determining SS. We report a novel epigenetic signature characterized by increased DNA methylation levels in a large number of genes enriched in pathways such as collagen metabolism and extracellular matrix organization. We identified potential new genetic variants associated with SS that might mediate their risk by altering DNA methylation or gene expression patterns, as well as disease-interacting genetic variants that exhibit regulatory function only in the SS population. Our study sheds new light on the interaction between genetics, autoantibody profiles, DNA methylation and gene expression in SS, and contributes to elucidate the genetic architecture of gene regulation in an autoimmune population.enAtribución 4.0 Internacionalhttp://creativecommons.org/licenses/by/4.0/AutoantibodiesEpigeneticAutoimmune diseasesGene expressionSjogren's syndromeGenetic variationAutoanticuerposEpigenómicaEnfermedades autoinmunesExpresión génicaSíndrome de SjögrenVariación genéticaMedical Subject Headings::Phenomena and Processes::Chemical Phenomena::Biochemical Phenomena::Biochemical Processes::DNA MethylationMedical Subject Headings::Check Tags::FemaleMedical Subject Headings::Phenomena and Processes::Genetic Phenomena::Genetic Processes::Gene ExpressionMedical Subject Headings::Phenomena and Processes::Genetic Phenomena::Genetic Processes::Gene Expression RegulationMedical Subject Headings::Chemicals and Drugs::Biological Factors::Antigens::Antigens, Surface::Histocompatibility Antigens::HLA AntigensMedical Subject Headings::Organisms::Eukaryota::Animals::Chordata::Vertebrates::Mammals::Primates::Haplorhini::Catarrhini::Hominidae::HumansMedical Subject Headings::Chemicals and Drugs::Amino Acids, Peptides, and Proteins::Peptides::Intercellular Signaling Peptides and Proteins::InterferonsMedical Subject Headings::Check Tags::MaleMedical Subject Headings::Diseases::Immune System Diseases::Autoimmune Diseases::Arthritis, Rheumatoid::Sjogren's SyndromeMedical Subject Headings::Chemicals and Drugs::Amino Acids, Peptides, and Proteins::Proteins::Blood Proteins::Immunoproteins::Immunoglobulins::AntibodiesMedical Subject Headings::Disciplines and Occupations::Natural Science Disciplines::Biological Science Disciplines::Biology::Genetics::Genomics::EpigenomicsMedical Subject Headings::Phenomena and Processes::Genetic Phenomena::Genetic VariationMedical Subject Headings::Phenomena and Processes::Genetic Phenomena::Genetic Processes::Gene Expression Regulation::Epigenesis, GeneticMedical Subject Headings::Diseases::Immune System Diseases::Autoimmune Diseasesresearch article34857786Acceso abierto10.1038/s41598-021-01324-02045-2322PMC8640069