Re-applying our pipeline revealed significant enrichment of ALS-associated genetic variants within CAV1 and CAV2 enhancers compared to the discovery cohort (n = 4,495, Data-Freeze-1; CAV1: p = 2.64 × 10−9, SKAT-O, 112 variants; CAV2: p = 7.30 × 10−8, SKAT-O, 174 variants) and replication cohort (n = 1,685, Data-Freeze-2; CAV1: p = 8.6 × 10−5, SKAT-O, 94 variants; CAV2: p = 4.87 × 10−7, SKAT-O, 150 variants). This evidence concerns the gene CAV1 and amyotrophic lateral sclerosis.