Date: Monday, October 22, 2018
Session Type: ACR Poster Session B
Session Time: 9:00AM-11:00AM
Systemic Sclerosis (SSc) is a complex systemic autoimmune disorder characterized by fibrosis of the skin and internal organs. Genetics and environmental factors contribute both to the etiology of the disease. Most variants discovered by GWAS locate in non-coding regions, which impedes immediate interpretation. Expression quantitative trait locus (eQTL) mapping is one tool to discover the molecular mechanisms by which SSc- genetic variants exert their risk.
In this study, we performed genome-wide eQTL analysis using GWAS and RNA-Seq data derived from whole blood samples of 220 SSc patients and 325 healthy control subjects. All samples analyzed are of European ancestry and form part of the PRECISESADs project dataset. We used matrixEQTL with 8 cofactors to condition on batch, RIN, age, sex, medication, fever, genetic background and blood cell composition.
We show that SSc-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 SSc-eQTL variants. Interestingly, in SSc patients we found two independent variants, which affect expression levels of the SPARC gene an effect not seen in control subjects. SPARC is overexpressed in SSc and related to the profibrotic effect of TGFbeta. We modeled the expression of SPARC using both variants and assessed the variance explained.
Our results will show how SSc context-specificity works at the molecular level and serve to illustrate the possible regulatory downstream effects of risk variants. This will ultimately inspire the generation of new hypotheses needed to increase our understanding of the biology of SSc and autoimmunity.
To cite this abstract in AMA style:Kerick M, Gonzalez Serna D, Teruel M, Babaei S, Acosta-Herrera M, Carnero-Montoro E, Makowska Z, Buttgereit A, Barturen G, Hayat S, Kageyama J, Martínez-Bueno M, Clinical Consortium P, Lesche R, Alarcón-Riquelme M, Martin J. Expression Quantitative Trait Loci -eQTL- Analysis in Systemic Sclerosis [abstract]. Arthritis Rheumatol. 2018; 70 (suppl 10). https://acrabstracts.org/abstract/expression-quantitative-trait-loci-eqtl-analysis-in-systemic-sclerosis/. Accessed October 1, 2022.
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