An integrative multi-omics approach in Sjögren’s Syndrome identifies novel genetic drivers with regulatory function and disease-specificity - Archive ouverte HAL Accéder directement au contenu
Pré-Publication, Document De Travail Année : 2021

An integrative multi-omics approach in Sjögren’s Syndrome identifies novel genetic drivers with regulatory function and disease-specificity

Résumé

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 identified vast coordinated hypomethylation and overexpression effects, that also exhibit increased variability, in many already known IFN-regulated genes. We report a novel epigenetic signature characterized by increased DNA methylation levels in a large number of novel genes enriched in pathways such as collagen metabolism and extracellular matrix organization. We identified new genetic variants associated with SS that 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, DNA methylation, gene expression and SS, and contributes to elucidate the genetic architecture of gene regulation in an autoimmune population.

Domaines

Immunologie

Dates et versions

hal-03115524 , version 1 (19-01-2021)

Identifiants

Citer

María Teruel, Guillermo Barturen, Manuel Martínez-Bueno, Miguel Barroso, Olivia Castelli, et al.. An integrative multi-omics approach in Sjögren’s Syndrome identifies novel genetic drivers with regulatory function and disease-specificity. 2021. ⟨hal-03115524⟩
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