Fig. 1

A Schematic representation of microRNA transcription and microRNA–mRNA interaction. microRNAs are transcribed from DNA sequences and processed by DROSHA from the primary structure to precursor structure and by Dicer into the mature sequence. These processed mature microRNA sequences then interact with mRNA targets, leading to mRNA degradation or translational repression. B microRNA precursor secondary structure. Altogether, we identified SNPs which are located within precursor, mature and 5-kb microRNA flanking regions. C Flowchart summarising our microRNA exploration procedure. We used summary statistics from the largest MS GWAS meta-analysis [6] and two publically available datasets to investigate microRNA-associated variation in MS. To capture variation within human microRNAs, we extracted the genomic coordinates of human microRNA precursor and mature regions from miRBase v22 and intersected these with all human variants recorded in dbSNP v151. In addition, we extended the precursor regions by 5 kb up- and downstream to incorporate SNPs within regulatory features (D). Overall, among the SNPs tested in the IMSGC’s meta-analysis, we identified 314 SNPs within microRNA precursor/mature regions and 36,841 SNPs in 5-kb flanking regions. D In our prioritisation process, we identified microRNA SNPs (1) among known MS susceptibility SNPs, (2) in strong Linkage Disequilibrium (LD) with known MS risk SNPs and (3) which meet the adjusted p value threshold for the 314 microRNA SNPs tested in the IMSGC meta-analysis. A and D adapted from “microRNA in Cancer” and “The Principle of a Genome-wide Association Study (GWAS)” in Biorender.com (2022). Retrieved from https://app.biorender.com/biorender-templates