Session Type: ACR Poster Session C
Session Time: 9:00AM-11:00AM
Systemic autoimmune diseases (SADs) are chronic inflammatory conditions with autoimmune aetiology and many common clinical features, hampering diagnosis and adequate treatment decisions. Finding new treatments or applying the existing ones in a more effective way is especially hard in SADs due to the heterogeneity of molecular mechanisms within the same disease class. Furthermore, most variants discovered by GWAS locate in non-coding regions, making it difficult for immediate interpretation. An important tool to discover the molecular mechanisms by which SADs- genetic variants exert their risk is the use of Expression Quantitative Trait Loci (eQTL) mapping.
We performed eQTL analysis using GWAS and RNA-Seq data derived from whole blood samples from ~1100 patients distributed across 7 different clinical entities (rheumatoid arthritis, systemic lupus erythematosus, systemic sclerosis, primary Sjögren ́s syndrome, primary antiphospholipid antibody syndrome, mixed connective tissue disease and undifferentiated connective tissue disease) and ~300 healthy individuals. All samples analyzed are of European ancestry and form part of the PRECISESADs project dataset. We used matrixEQTL with 8 cofactors to correct for bias introduced by batch, RIN, age, sex, medication, fever, genetic background and blood cell composition.
We show that SADs-associated variants have widespread effects on genome-wide DNA expression levels. By means of stratified and interaction analyses we further show the gender and disease-specific context of SADs-eQTL variants. Importantly > 85% of eQTLs were found in patients but not in healthy subjects and shared across diseases, suggesting how SADs context-specificity works at the molecular level.
Our work serves to illustrate the possible regulatory downstream effects of risk variants and will ultimately inspire the generation of new hypotheses needed to increase our limited understanding on the biology of autoimmunity.
To cite this abstract in AMA style:Kerick M, Gonzalez Serna D, Carnero-Montoro E, Babaei S, Acosta-Herrera M, Teruel M, Barturen G, Makowska Z, Buttgereit A, Hayat S, Kageyama J, Martínez-Bueno M, Clinical Consortium P, Lesche R, Martin J, Alarcón-Riquelme M. eQTL Analysis of More Than 1000 Human Blood Samples Reveals Shared and Unique Signals across Seven Systemic Autoimmune Diseases : The Precisesads Project [abstract]. Arthritis Rheumatol. 2018; 70 (suppl 9). https://acrabstracts.org/abstract/eqtl-analysis-of-more-than-1000-human-blood-samples-reveals-shared-and-unique-signals-across-seven-systemic-autoimmune-diseases-the-precisesads-project/. Accessed November 29, 2022.
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ACR Meeting Abstracts - https://acrabstracts.org/abstract/eqtl-analysis-of-more-than-1000-human-blood-samples-reveals-shared-and-unique-signals-across-seven-systemic-autoimmune-diseases-the-precisesads-project/