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) (Fig. 1A; Supplemental Data). This evidence concerns the gene TARDBP and amyotrophic lateral sclerosis.