Figure 1.

Schematic illustration of the analytical workflow

The genetic risk score for sporadic ALS was generated using large cohorts as the reference and training sets. This general ALS genetic risk score was then calculated for a sizable cohort of C9orf72 carriers. Follow-up analyses included pathway analysis and the identification of individual loci with a major contribution to the age at onset. Using the information obtained from these genetic analyses, we performed drug repurposing based on gene-gene-pattern matching and expression-pattern matching to identify drugs that may delay symptom onset among C9orf72 carriers. In vitro drug validation confirmed the neuroprotective effect of the drug nominated by this approach.