We investigated the regulatory roles of a high-confidence and reproducible set of 69 trait-relevant lincRNAs (TR-lincRNAs) in human lymphoblastoid cells whose biological relevance is supported by their evolutionary conservation during recent human history and genetic interactions with other trait-associated loci.
Pathophysiological relevance is supported by data demonstrating that early and high circulating levels of IL-6 are associated with increased mortality [ 9].
An upregulation of PON2 and its relevance are supported by recent studies that found high PON2 levels in association with poor prognosis in cohorts of pediatric ALL or with imatinib resistance in CML patients.
Nevertheless, we succeeded in isolating thirteen of the 50 most frequent TCCs in L-III, and their relevance is supported by the presence of four of them in another brain region.
The relevance of our selection was supported by the fact that ribavirin, an already known influenza virus inhibitor, was identified with a negative enrichment of -0.83 and a pvalue of 0.00157.
Biological relevance towards asthma physiopathology was supported by gene expression analysis of experimental asthma mouse models and literature-based functional studies of annotated genes for many of the candidate genetic loci.
The health relevance of the patterns was supported by expected correlations with a broad set of criteria such as depression, well-being, sickness, absence, blood pressure, heart rate, type-A behaviour or burnout.
The biological relevance of these findings was supported by mechanistic experiments demonstrating the roles of CD8+ lymphocytes or interferon-gamma in bile duct injury in a mouse model of biliary atresia [ 6- 8].
The general relevance of this module was supported by highly significant enrichment of genetic variants identified by all GWAS and cancer studies, as well as known diagnostic and therapeutic targets.
The biological relevance of the genes identified was supported by two independent sources, namely differential expression in the microarray experiment analyzed and known disease associations based on genetic screening or mechanistic studies.
Their relevance for the infection process was supported by a Gene Ontology (GO) analysis.
