Postulating that there are additional genetic risk variants other than the MTHFR C677T variant that elevate plasma homocysteine levels and thus increase risk for ischemic stroke, we performed a comprehensive genetic association study of the homocysteine metabolic pathway by investigating 25 homocysteine metabolic pathway genes in well-characterized ischemic stroke cases and matched controls of Singaporean Chinese ethnicity. The gene discussed is MTHFR; the disease is ischemic stroke.