Resolution for gene-based analysis was assessed by comparing the number of missense and loss-of-function variants in previously identified ALS genes (i.e., SOD1, FUS, TARDBP, KIF5A, NEK1 and C21orf2) present in ExAC to the number of variants tested in our gene-based analysis (Supplementary Table 5). The gene discussed is FUS; the disease is amyotrophic lateral sclerosis.