Re-applying our pipeline to CAV1 Hi-C-derived CNS enhancers in the validation cohort revealed significant enrichment of ALS-associated genetic variation (p = 0.03; SKAT-O; 51 variants; Table S3); 60 (3.6%) ALS patients carried an ALS-associated CAV1 CNS enhancer risk variant compared to 3 (0.7%) of controls (risk ratio = 5.1). Here, CAV1 is linked to amyotrophic lateral sclerosis.