Shared Gene Expression Between Multiple Sclerosis and Ischemic Stroke

Abstract

Patients with multiple sclerosis (MS) appear to have an increased risk of ischemic stroke (IS). Although MS and IS have very different phenotypes, gene-based and pathway-based analyses of large-scale genome-wide association studies (GWAS) have increasingly enhanced our understanding of these two diseases. Whether there are common molecular mechanisms connecting MS and IS is still unclear. Here, we describe the outcome of gene-based test and pathway-based analysis of GWAS datasets that explored potential gene expression links between MS and IS. After identifying significant gene sets individually of MS and IS, we performed pathway-based analysis in four biological pathway databases (KEGG, PANTHER, REACTOME, and WikiPathways) and GO categories. We discovered that there were 9 shared pathways between MS and IS in KEGG, 2 in PANTHER, 14 in REACTOME, 1 in WikiPathways, and 194 in GO annotations (p < 0.05). These results provide an improved understanding about possible shared mechanisms and treatments strategies for MS and IS. They also provide some basis for further studies of how these two diseases are linked at the molecular level.

Keywords: gene-based test; genome-wide association studies; histocompatibility complex variants; ischemic stroke; multiple sclerosis; pathway-based analysis; single nucleotide polymorphism.

Figure 1

Flow diagram of the three-phase analysis design. In phase I, we performed a gene-based test using the MS dataset from IMSGC and the IS GWAS dataset from METASTROKE. Gene sets identified with p < 0.05 were carried forward to the next phase. In phase II, we carried out a pathway-based analysis for the two diseases. In phase III, shared and significant pathways were identified that had p's < 0.05.

Figure 2

Interactive networks between MS and IS. Shared and significant biological process (A), cellular component (B), and molecular function (C) from GO function annotation. Bubble color indicates the p-value of each annotation; line width indicates the degree of similarity; arrows represent common affiliations between them.

Figure 3

Pathway analysis. Shared and significant, non-redundant GO annotations. Enriched clusters between MS and IS, including the –log10 (P-value), are shown.