ALS exhibited extensive causal associations, with genetically predicted increased expression of NRDC (OR: 1.084; 95% CI: 1.048–1.122; p = 2.89 × 10−6), BCL2L13 (OR: 1.065; 95% CI: 1.037–1.094; p = 3.41 × 10−6), and D2HGDH (OR: 1.165; 95% CI: 1.116–1.216; p = 2.50 × 10−12) associated with elevated risk, indicating contributions from protein processing, apoptosis regulation, and organic acid metabolism to motor neuron degeneration. Here, D2HGDH is linked to Motor neuron atrophy.