Primary Sjogrens 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

中文翻译：

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Sjogrens综合征的综合多组学方法可识别具有调节功能和疾病特异性的新型遗传驱动因素

原发性干燥综合征（SS）是一种全身性自身免疫性疾病，其特征是淋巴细胞浸润以及外分泌唾液和泪腺受损。SS的病因复杂，涉及环境触发因素和遗传因素。通过进行综合的多组学研究，我们在许多已知的IFN调控基因中鉴定出了巨大的协同低甲基化和过表达效应，这些效应还表现出增加的变异性。我们报告了一个新颖的表观遗传学特征，其特征是在大量新基因中丰富了DNA甲基化水平，这些新基因丰富了诸如胶原蛋白代谢和细胞外基质组织等途径。我们发现了与SS相关的新遗传变异，它们通过改变DNA甲基化或基因表达模式来介导其风险，以及仅在SS人群中发挥调节功能的与疾病相互作用的遗传变异。我们的研究为遗传学，DNA甲基化，基因表达和SS之间的相互作用提供了新的思路，并有助于阐明自身免疫人群中基因调控的遗传结构。