GWAS-associated Variants, Non-genetic Factors and Transient Transcriptome in Multiple Sclerosis Etiopathogenesis: a Colocalization Analysis

About: This article is published in Journal of the Neurological Sciences.The article was published on 2021-03-12 and is currently open access. It has received 0 citations till now. The article focuses on the topics: Transcriptome.

Figures

Figure 4. A comprehensive genomic atlas on gene-environment interactions regulating transcription in MS. (A), Searchable results at mscoloc.com derive from the matches of GWAS

Figure 1. GWAS-associated SNP distribution across genomic partitions and their distance relative to the transcription starting site (TSS). Panel A, Multiple Sclerosis; B, Immune-mediated

Table 1. Enrichment of MS-associated genetic variants in lists of T-cell transient transcripts extracted from Michel et al. (21). The whole transcriptome list was split in two sub-lists depending on the transcripts’ half-life: short (<60’) and long (≥60’), respectively. Results are considered significant at p<0.05 and are highlighted in bold.

Figure 2. Enrichment of MS-associated SNPs in databases of regulatory elements, sorted by experiment/cell lines. X-axis shows the Odd Ratio, y-axis shows the -log (pValue); dot size is proportional to the support of each match, i.e., the number of hits resulting from the colocalization analysis. Color of each point is related to the Harmonic Score (HS), a comprehensive estimation of the relevance of hits, as derived by merging and balancing the OR, pValue and Support of each match. Thus, prioritized hits are represented by the darker dots that occupy the upper-right area of the chart. Labeled points have HS>40. Labels were arbitrarily designated according to the database of origin and the cell lineage where the enrichment occurred.

Table 2. Enrichment of MS-GWAS regions (at ±50,100,200 kb range of extension) in lists (number in brackets in the right-most column) of DNA binding sites of human and viral molecular transducers; significant results (p<0.05, corresponding to a -log (p)>1.301) in bold.

Figure 3. Colocalization analysis of DBRs for human and viral molecular transducers, MSassociated SNPs and DNA regulatory regions derived from databases. (A),Schematic representation of the colocalization analysis. (ROI: Region of interest; DBR: DNA Binding Regions; ENCODE TFBS: Transcription Factor Binding Site). The figure shows the tracks we considered for the colocalization analyses. In brief, the ROI included the DBRs of MS-related viral and human transducers and was matched with MS-associated SNPs extended by 50, 100, and 200 kilobases that colocalize with regions plausibly coding for trRNAs (Database). As a control (Universe), we took from ENCODE the entire list of transcription factors binding sites. Results were considered significant if a colocalization was found across ROI and a Databases element