This has led to testing of various genotype-guided dosing protocols. A 12-week randomized trial of 455 patients treated with warfarin showed significantly more time in therapeutic range for the international normalized ratio (INR) for patients assigned to the genotype-guided dosing regimen versus stan- A 4-week ran- domized trial of 1015 patients treated with warfarin showed no significant difference in the time in therapeutic range for the A 12-week randomized trial of 548 patients treated with acenocoumarol or phencou- mon showed no significant difference in the time in therapeu- tic range for the INR (61.6% versus 60.2%; P=0.52).81 A genome-wide association study of individuals taking 80 mg simvastatin identified common variants on SLCO1B1 that are associated with myopathy.82 This may prove useful in screening for patients being considered for simvastatin therapy, although randomized validation studies demonstrat- ing the clinical and cost-effectiveness of its use are lacking. Several monogenic disorders are associated with stroke. Although rare, their effect on the individual patient is substan- tial because individuals carrying a mutation are likely to develop stroke or other clinical characteristics of disease. Thus, iden- tification of the underlying gene for these disorders is impor- tant for diagnosis, counseling, and patient management. With the exception of sickle cell disease (SCD; discussed below), no treatment based specifically on genetic factors has yet been shown to reduce incident stroke. Cerebral autosomal-dominant arteriopathy with subcortical infarcts and leukoencephalopa- thy is characterized by subcortical infarcts, dementia, migraine headaches, and white matter changes that are readily apparent on brain magnetic resonance imaging (MRI).83 Cerebral autoso- mal-dominant arteriopathy with subcortical infarcts and leuko- encephalopathy is caused by any one of a series of mutations in Genetic testing for NOTCH3 mutations is available. 