21 FRGs (NR4A1, CYBB, DRD4, SETD1B, LAMP2, ACSL4, MYB, PROM2, CHMP5, ULK1, AKR1C2, TGFBR1, TMBIM4, MLLT1, PSAT1, HIF1A, LINC00336, AMN, SLC38A1, CISD1, and GABARAPL2) in the primary data and 16 FRGs in the blood data (NR4A1, DRD4, SETD1B, MYB, PROM2, CHMP5, ULK1, AKR1C2, TGFBR1, TMBIM4, MLLT1, HIF1A, LINC00336, IL33, SLC38A1, and CISD1) were identified as target genes by using LASSO analysis, which signature showed better prediction ability in distinguishing ALS from controls. The gene discussed is SETD1B; the disease is amyotrophic lateral sclerosis.