Teruel, MaríaBarturen, GuillermoMartínez Bueno, ManuelCastellini Pérez, OliviaBarroso Gil, MiguelPovedano, ElenaKerick, MartinCatalà Moll, FrancescMakowska, ZuzannaButtgereit, AnneBeretta, LorenzoKniesch, KatjaLi, TianluLópez Pedrera, CharyMakowska, ZuzannaMarañón, ConcepciónMuchmore, BrianNeves, EsmeraldaRouvière, BénédicteSimon, QuentinTrombetta, ElenaVarela, NievesWitte, TorstenPers, Jacques-OlivierMarañón, ConcepciónBallestar Tarín, EstebanMartin, JavierCarnero Montoro, ElenaAlarcón Riquelme, MartaPRECISESADS Clinical ConsortiumPRECISESADS Flow Cytometry Study GroupVigone, BarbaraSaraux, AlainDevauchelle-Pensec, ValérieCornec, DiviJousse-Joulin, SandrineLauwerys, BernardDucreux, JulieMaudoux, Anne-liseVasconcelos, CarlosTavares, AnaNeves, EsmeraldaFaria, RaquelBrandão, MarianaCampar, AnaMarinho, AntónioFarinha, FátimaAlmeida, IsabelGonzalez-Gay Mantecón, Miguel ÁngelBlanco Alonso, RicardoCorrales Martínez, AlfonsoCervera i Segura, Ricard, 1960-Rodríguez Pintó, IgnasiEspinosa Garriga, GerardLories, RikLanghe, Ellen deHunzelmann, NicolasBelz, DoreenWitte, TorstenBaerlecken, NiklasStummvoll, GeorgZauner, MichaelLehner, MichaelaCollantes, EduardoOrtega Castro, RafaelaAguirre Zamorano, Mª. ÁngelesEscudero Contreras, AlejandroCastro Villegas, Mª CarmenOrtego, NorbertoFernández Roldán, María ConcepciónRaya, EnriqueJiménez Moleón, InmaculadaRamon, Enrique deDíaz Quintero, IsabelMeroni, Pier LuigiGerosa, MariaSchioppo, TommasoArtusi, CarolinaChizzolini, CarloZuber, AleksandraWynar, DonatienneKovács, LaszlóBalog, AttilaDeák, MagdolnaBocskai, MártaDulic, SonjaKádár, GabriellaHiepe, FalkGerl, VeliaThiel, SilviaRodriguez Maresca, ManuelLópez Berrio, AntonioAguilar Quesada, RocíoNavarro Linares, HéctorAlvarez, MontserratÁlvarez Errico, DamianaAzevedo, NancyBarbarroja, NuriaButtgereit, AnneCheng, QingyuChizzolini, CarloCremer, JonathanGroof, Aurélie deLanghe, Ellen deDucreux, JulieDufour, AleksandraGerl, VeliaHernández Fuentes, MaríaKhodadadi, Laleh2022-01-272022-01-272021-12-012045-2322https://hdl.handle.net/2445/182722Primary 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.18 p.application/pdfengcc by (c) Teruel, María et al, 2021http://creativecommons.org/licenses/by/3.0/es/Malalties autoimmunitàriesEpigenèticaAutoimmune diseasesEpigeneticsinfo:eu-repo/semantics/article2022-01-25info:eu-repo/semantics/openAccess34857786