Genetically predicted plasma levels of amino acids and stroke risk: a Mendelian randomization study

Stroke, including ischemic stroke (IS) and small vessel stroke (SVS), is a major cause of morbidity and mortality globally. The role of amino acids remains underexplored in the risk and outcomes of stroke. In the present study, the causal effects of genetically determined amino acid levels on stroke and its functional outcomes were investigated using Mendelian randomization (MR). Data was analyzed by single nucleotide polymorphisms (SNPs), Inverse-variance weighted (IVW), etc. The results of False Discovery Rate (FDR) correction show that higher genetically determined levels of CSF glycine, glutamate, glutamine, and phenylalanine are associated with increased risks of SVS (odds ratios [OR]: 1.34, 1.48, 1.58, and 1.58, respectively; 95 % confidence intervals [CI]: 1.14-1.56, 1.17-1.87, 1.29-1.94, and 1.32-1.89; P-values: 2.46 × 10^-4, 9.50 × 10^-4, 1.30 × 10^-5, and 7.37 × 10^-7). Higher phenylalanine levels were associated with poor functional outcomes after ischemic stroke, defined as a modified Rankin Scale score ≥ 3 (OR per SD increase: 1.79; 95 % CI: 1.26-2.55; P = 1.15 × 10^-3). These findings suggest that amino acids can serve as potential biomarkers and therapeutic targets for stroke.