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Additional 1 H-MRS studies using higher magnetic field strengths and optimal measurements of metabolite concentrations and ratios are needed to establish specificity and sensitivity of the Glx/NAA and GABA/Glx ratios for ALS Longitudinal studies are needed to understand how these ratios change throughout ALS disease progression and compare to patients with other neurological syndromes Greater volumes of studies measuring glutathione are needed to better understand the relation to disease progression in ALS 13 C MRS and DMI studies in ALS patients could provide greater sensitivity for changes in mitochondrial energetics through measurement of metabolite flux (V TCA and V cycleGlu )

Furthermore, several of the loci identified here overlap or fall near signals reported in prior global glaucoma GWAS, while others may reflect novel ancestry-specific contributions, reinforcing the value of expanding genomic studies in underrepresented populations