Fig. 3.

Exercise-induced pathways are enriched with ALS genetic risk.

(a) Transcriptome analysis of peripheral blood mononuclear cells (PBMCs) reveals that biological pathways differentially expressed following acute exercise are significantly enriched with ALS-associated rare variants. The pathways depicted pass multiple testing correction (FDR<0.05). (b) Differentially expressed biological pathways are closely related to neuronal health. Broadly, the roles of fibroblast growth factor (FGF) and nerve growth factor (NGF) pathways are cell proliferation, apoptosis and cell survival, cell differentiation and cell migration. The NGF and FGF pathways are significantly related to ALS and are enriched following acute exercise. In ALS, it is possible that mutation in these pathways leads to deranged differential expression in response to hypoxia, oxidative stress and starvation during exercise and this may precipitate damage to motor neurons. (c) ALS risk genes which are differentially expressed in response to exercise are shown with fold change and significance.