Open AccessExploring the overlap between rheumatoid arthritis susceptibility loci and long non-coding RNA annotations
Author(s) -
James Ding,
Chenfu Shi,
John Bowes,
Stephen Eyre,
Gisela Orozco
Publication year - 2020
Publication title -
plos one
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.99
H-Index - 332
ISSN - 1932-6203
DOI - 10.1371/journal.pone.0223939
Subject(s) - biology , enhancer , immune system , genetics , computational biology , long non coding rna , mechanism (biology) , phenotype , rheumatoid arthritis , rna , gene , immunology , transcription factor , philosophy , epistemology
Whilst susceptibility variants for many complex diseases, such as rheumatoid arthritis (RA), have been well characterised, the mechanism by which risk is mediated is still unclear for many loci. This is especially true for the majority of variants that do not affect protein-coding regions. lncRNA represent a group of molecules that have been shown to be enriched amongst variants associated with RA and other complex diseases, compared to random variants. In order to establish to what degree direct disruption of lncRNA may represent a potential mechanism for mediating RA susceptibility, we chose to further explore this overlap. By testing the ability of annotated features to improve a model of disease susceptibility, we were able to demonstrate a local enrichment of enhancers from immune-relevant cell types amongst RA susceptibility variants (log 2 enrichment 3.40). This was not possible for lncRNA annotations in general, however a small, but significant enrichment was observed for immune-enriched lncRNA (log 2 enrichment 0.867002). This enrichment was no longer apparent when the model was conditioned on immune-relevant enhancers (log 2 enrichment -0.372734), suggesting that direct disruption of lncRNA sequence, independent of enhancer disruption, does not represent a major mechanism by which susceptibility to complex diseases is mediated. Furthermore, we demonstrated that, in keeping with general lncRNA characteristics, immune-enriched lncRNA are expressed at low levels that may not be amenable to functional characterisation.