Larsson SC, et al. - Using Mendelian randomization, researchers ascertained whether circulating levels of total homocysteine (tHcy) and B vitamins are selectively correlated with small vessel stroke (SVS), but not with other stroke subtypes. For this investigation, summary statistics data were used for single-nucleotide polymorphisms related to 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 non-cases). In genetically predicted levels of folate and vitamin B₆, the odds ratio of SVS per 1 SD increased were 0.49 and 0.70. Findings suggested no association of genetically higher vitamin B12 levels with any stroke subtype. Investigators suggested that any effect of treatment with homocysteine reduction in stroke prevention is limited to the SVS subtype. Whether genetic variants at MTHFR and MUT genes influence SVS risk via pathways other than homocysteine levels and downstream effects require further research.