2010; Bowden and Vansteelandt 2011). For example, in an investigation into the possible causal effect of homocysteine level on stroke risk, the odds ratio for the genotype-stroke (G–Y) association, using a dichotomisation of the MTHFR C677T polymorphism into TT and CC carriers as a genetic IV, was found to be significant at 1.26 with 95 % CI (1.14, 1.40) (Casas et al. 2005). The gene discussed is MTHFR; the disease is Stroke.