Collapsing analysis of all rare functional variants (missense and protein truncating variants) (Supplemental Table 2) found genome-wide and study-wide significant (p < 4.9 × 10−7) case-enrichment for known ALS genes SOD1, TARDBP, TBK1 (OR=19.18, p = 3.67 × 10−39; OR=4.73, p = 2 × 10−10; OR=2.3, p = 7.49 × 10−9, respectively) and control-enrichment for ALKBH3 (OR=0.26, p = 4.88 × 10−7) (Figure 1A; Supplemental Data). This evidence concerns the gene TBK1 and amyotrophic lateral sclerosis.