Integrative epigenomics in Sjögren´s syndrome reveals novel pathways and a strong interaction between the HLA, autoantibodies and the interferon signature

Abstract 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 stu...

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Autores principales:	María Teruel, Guillermo Barturen, Manuel Martínez-Bueno, Olivia Castellini-Pérez, Miguel Barroso-Gil, Elena Povedano, Martin Kerick, Francesc Català-Moll, Zuzanna Makowska, Anne Buttgereit, PRECISESADS Clinical Consortium, PRECISESADS Flow Cytometry Study Group, Jacques-Olivier Pers, Concepción Marañón, Esteban Ballestar, Javier Martin, Elena Carnero-Montoro, Marta E. Alarcón-Riquelme
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/3eee442ab7cc476caac7987d806bfc0e
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spelling	oai:doaj.org-article:3eee442ab7cc476caac7987d806bfc0e2021-12-05T12:15:50ZIntegrative epigenomics in Sjögren´s syndrome reveals novel pathways and a strong interaction between the HLA, autoantibodies and the interferon signature10.1038/s41598-021-01324-02045-2322https://doaj.org/article/3eee442ab7cc476caac7987d806bfc0e2021-12-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-01324-0https://doaj.org/toc/2045-2322Abstract 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.María TeruelGuillermo BarturenManuel Martínez-BuenoOlivia Castellini-PérezMiguel Barroso-GilElena PovedanoMartin KerickFrancesc Català-MollZuzanna MakowskaAnne ButtgereitPRECISESADS Clinical ConsortiumPRECISESADS Flow Cytometry Study GroupJacques-Olivier PersConcepción MarañónEsteban BallestarJavier MartinElena Carnero-MontoroMarta E. Alarcón-RiquelmeNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-18 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q María Teruel Guillermo Barturen Manuel Martínez-Bueno Olivia Castellini-Pérez Miguel Barroso-Gil Elena Povedano Martin Kerick Francesc Català-Moll Zuzanna Makowska Anne Buttgereit PRECISESADS Clinical Consortium PRECISESADS Flow Cytometry Study Group Jacques-Olivier Pers Concepción Marañón Esteban Ballestar Javier Martin Elena Carnero-Montoro Marta E. Alarcón-Riquelme Integrative epigenomics in Sjögren´s syndrome reveals novel pathways and a strong interaction between the HLA, autoantibodies and the interferon signature
description	Abstract 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.
format	article
author	María Teruel Guillermo Barturen Manuel Martínez-Bueno Olivia Castellini-Pérez Miguel Barroso-Gil Elena Povedano Martin Kerick Francesc Català-Moll Zuzanna Makowska Anne Buttgereit PRECISESADS Clinical Consortium PRECISESADS Flow Cytometry Study Group Jacques-Olivier Pers Concepción Marañón Esteban Ballestar Javier Martin Elena Carnero-Montoro Marta E. Alarcón-Riquelme
author_facet	María Teruel Guillermo Barturen Manuel Martínez-Bueno Olivia Castellini-Pérez Miguel Barroso-Gil Elena Povedano Martin Kerick Francesc Català-Moll Zuzanna Makowska Anne Buttgereit PRECISESADS Clinical Consortium PRECISESADS Flow Cytometry Study Group Jacques-Olivier Pers Concepción Marañón Esteban Ballestar Javier Martin Elena Carnero-Montoro Marta E. Alarcón-Riquelme
author_sort	María Teruel
title	Integrative epigenomics in Sjögren´s syndrome reveals novel pathways and a strong interaction between the HLA, autoantibodies and the interferon signature
title_short	Integrative epigenomics in Sjögren´s syndrome reveals novel pathways and a strong interaction between the HLA, autoantibodies and the interferon signature
title_full	Integrative epigenomics in Sjögren´s syndrome reveals novel pathways and a strong interaction between the HLA, autoantibodies and the interferon signature
title_fullStr	Integrative epigenomics in Sjögren´s syndrome reveals novel pathways and a strong interaction between the HLA, autoantibodies and the interferon signature
title_full_unstemmed	Integrative epigenomics in Sjögren´s syndrome reveals novel pathways and a strong interaction between the HLA, autoantibodies and the interferon signature
title_sort	integrative epigenomics in sjögren´s syndrome reveals novel pathways and a strong interaction between the hla, autoantibodies and the interferon signature
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/3eee442ab7cc476caac7987d806bfc0e
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Integrative epigenomics in Sjögren´s syndrome reveals novel pathways and a strong interaction between the HLA, autoantibodies and the interferon signature

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