Among the outlier genes that exhibited aberrations in both promoter accessibility and gene expression (Table S1), 12 have previously been associated with ALS: CDKL5, HIF1A, ABCA2, VPS4B, NOVA1, NRG1, NIPA1, BCL2, ALYREF, UBQLN2, IRAK4, and DDX3X. 1,5,7,11,45,46,47,48,49,50,51 In some cases, variants have been associated with ALS or pathways involving these genes are dysregulated. This evidence concerns the gene IRAK4 and amyotrophic lateral sclerosis.