Larsson SC, et al. - Using Mendelian randomization, researchers ascertained if small vessel stroke (SVS) is selectively associated with circulating total homocysteine (tHcy) and B vitamin levels, but not with other stroke subtypes. Summary statistics data were utilized for single-nucleotide polymorphisms (SNPs) associated with tHcy (n = 18), folate (n = 3), vitamin B6 (n = 1), and vitamin B12 (n = 14) levels, and the corresponding data for stroke from the MEGASTROKE consortium (n = 16,952 subtyped ischemic stroke cases and 404,630 noncases). The outcomes provide support for possible tHcy and folate level associations with SVS, and these relationships are specific to the SVS subtype. These findings suggest that any effect of homocysteine-lowering therapy will be confined to the SVS subtype in preventing stroke. Whether genetic variants at or near the genes of MTHFR and MUT affect SVS risk through pathways other than homocysteine levels and downstream effects needs further research.