Publication
Genome-wide whole blood transcriptome profiling in a large European cohort of systemic sclerosis patients.
Publisher:
BMJ
Date:
19-06-2020
DOI:
10.1136/ANNRHEUMDIS-2020-217116
Abstract: The analysis of annotated transcripts from genome-wide expression studies may help to understand the pathogenesis of complex diseases, such as systemic sclerosis (SSc). We performed a whole blood (WB) transcriptome analysis on RNA collected in the context of the European PRECISESADS project, aiming at characterising the pathways that differentiate SSc from controls and that are reproducible in geographically erse populations. S les from 162 patients and 252 controls were collected in RNA stabilisers. Cases and controls were ided into a discovery (n=79+163 Southern Europe) and validation cohort (n=83+89 Central-Western Europe). RNA sequencing was performed by an Illumina assay. Functional annotations of Reactome pathways were performed with the Functional Analysis of In idual Microarray Expression (FAIME) algorithm. In parallel, immunophenotyping of 28 circulating cell populations was performed. We tested the presence of differentially expressed genes athways and the correlation between absolute cell counts and RNA transcripts/FAIME scores in regression models. Results significant in both populations were considered as replicated. Overall, 15 224 genes and 1277 functional pathways were available of these, 99 and 225 were significant in both sets. Among replicated pathways, we found a deregulation in type-I interferon, Toll-like receptor cascade, tumour suppressor p53 protein function, platelet degranulation and activation. RNA transcripts or FAIME scores were jointly correlated with cell subtypes with strong geographical differences neutrophils were the major determinant of gene expression in SSc-WB s les. We discovered a set of differentially expressed genes athways validated in two independent sets of patients with SSc, highlighting a number of deregulated processes that have relevance for the pathogenesis of autoimmunity and SSc.