Genome-wide association studies have identified novel genetic variants influencing risk of stroke. A meta-analysis of genome-wide association studies from prospective cohorts identified a locus on 12p13 near the NINJ2 gene associated with incident ischemic stroke,71 but large case-control studies have not replicated this finding.72,73 This inconsistency may be because of a possible effect of this locus on stroke mortality,74 a synthetic association from rare variants not well represented in the subsequent replication studies, or a false-positive asso- ciation. Recent meta-analyses of large case-control studies have identified novel genetic associations with specific stroke subtypes, suggesting that risk factor profiles and pathologi- cal mechanisms may differ across subtypes. Two loci have been associated with large-vessel stroke in individuals of European ancestry: a locus on 6p21.175 and a locus on 7q21 Meschia et al Guidelines for the Primary Prevention of Stroke 3759 near the HDAC9 gene, encoding a protein involved in histone A variant in the PRKCH gene encoding a protein kinase has been associated with small-vessel stroke The genetic variants described to date account for only a small proportion of stroke risk. Even combined, their predictive value is likely to be low. Personalizing medicine through genetic testing has the potential to improve the safety of primary prevention pharma- cotherapies. For example, genetic variability in cytochrome (VKORC1), and rare missense mutations in the factor IX pro- peptide affect sensitivity of patients to vitamin K antagonists. This has led to testing of various genotype-guided dosing protocols. 