RT Journal Article
T1 Integrative epigenomics in Sjögren´s syndrome reveals novel pathways and a strong interaction between the HLA, autoantibodies and the interferon signature
A1 Teruel, María
A1 Barturen, Guillermo
A1 Martínez-Bueno, Manuel
A1 Castellini-Pérez, Olivia
A1 Barroso-Gil, Miguel
A1 Povedano, Elena
A1 Kerick, Martin
A1 Català-Moll, Francesc
A1 Makowska, Zuzanna
A1 Buttgereit, Anne
A1 Pers, Jacques-Olivier
A1 Marañón, Concepción
A1 Ballestar, Esteban
A1 Martin, Javier
A1 Carnero-Montoro, Elena
A1 Alarcón-Riquelme, Marta E.
K1 Autoantibodies
K1 Epigenetic
K1 Autoimmune diseases
K1 Gene expression
K1 Sjogren's syndrome
K1 Genetic variation
K1 Autoanticuerpos
K1 Epigenómica
K1 Enfermedades autoinmunes
K1 Expresión génica
K1 Síndrome de Sjögren
K1 Variación genética
AB Primary 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.
PB Springer Nature
YR 2021
FD 2021-12-02
LK http://hdl.handle.net/10668/4558
UL http://hdl.handle.net/10668/4558
LA en
NO Teruel 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):23292
DS RISalud
RD Apr 11, 2025