TY  - GEN
TI  - Integrative epigenomics in Sjögren´s syndrome reveals novel pathways and a strong interaction between the HLA, autoantibodies and the interferon signature
AU  - Teruel Artacho, María
AU  - Barturen Briñas, Guillermo
AU  - Martínez Bueno, Manuel
AU  - Castellini Pérez, Olivia
AU  - Barroso Gil, Miguel
AU  - Povedano Espejo, Elena
AU  - Kerick, Martin
AU  - Marañón Lizana, Concepción
AU  - Martín Ibáñez, Javier
AU  - Carnero Montoro, Elena
AU  - Alarcón Riquelme, Marta Eugenia
AU  - Castro Villegas, Mª Carmen
AU  - Ortego Centeno, Norberto
AU  - Fernández Roldán, María Concepción
AU  - Raya Álvarez, Enrique Germán
AU  - Jiménez Moleón, Inmaculada
AU  - Rodríguez Maresca, Manuel
AU  - López Berrio, Antonio
AU  - Aguilar Quesada, Rocío
AU  - Navarro Linares, Héctor
AU  - Muchmore, Brian
AU  - PRECISESADS Clinical Consortium
AU  - PRECISESADS Flow Cytometry Study Group
PY  - 2021
PB  - Nature
LA  - eng
AB  - Funding for the preparation of this manuscript has received support from the Innovative Medicines Initiative Joint Undertaking under grant agreement no 115,565, resources composed of the financial contribution from the European Union's Seventh Framework Program (FP7/2007-2013) and the EFPIA companies' in kind contribution. MT is supported by a Spanish grant from Health Department, Junta de Andalucia (PI/0017/2016) and through the Innovative Medicines Initiative 2 Joint Undertaking under grant agreement No 806975. This Joint Undertaking receives support from the European Union's Horizon 2020 research and innovation programme and EFPIA. EC-M was funded by the Postdoctoral Training Subprogramme Juan de la Cierva-Ministry of Economy and Competitiveness (FJCI_2014_20652). We thank Ralf Lesche for the production of RNASeq data and Marc Torres Ciuro for design support. ; 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. ; Innovative Medicines Initiative Joint Undertaking from the European Union's Seventh Framework Program (FP7/2007-2013) 115,565 ; EFPIA companies ; Junta de Andalucia PI/0017/2016 ; Innovative Medicines Initiative 2 Joint Undertaking 806975 European Union's Horizon 2020 research and innovation programme ; EFPIA ; Postdoctoral Training Subprogramme Juan de la Cierva-Ministry of Economy and Competitiveness FJCI_2014_20652
UR  - http://hdl.handle.net/10481/72314
DO  - 10.1038/s41598-021-01324-0
UR  - https://www.pollux-fid.de/r/base-ftunivgranada:oai:digibug.ugr.es:10481/72314
H1  - Pollux (Fachinformationsdienst Politikwissenschaft)
ER  -