Common variation in PHACTR 1 is associated with susceptibility to cervical artery dissection

Cervical artery dissection (CeAD), a mural hematoma in a carotid or vertebral artery, is a major cause of ischemic stroke in young adults although relatively uncommon in the general population (incidence of 2.6/ 00,000 per year) . Minor cervical traumas, infection, migraine and hypertension are putative risk factors –3, and inverse associations with obesity and hypercholesterolemia are described3,4. No confirmed genetic susceptibility factors have been identified using candidate gene approaches5. We performed genome-wide association studies (GWAS) in ,393 CeAD cases and 4,4 6 controls. The rs9349379[G] allele (PHACTR1) was associated with lower CeAD risk (odds ratio (OR) = 0.75, 95% confidence interval (CI) = 0.69–0.82; P = 4.46 × 0− 0), with confirmation in independent follow-up samples (659 CeAD cases and 2,648 controls; P = 3.9 × 0−3; combined P = .00 × 0− ). The rs9349379[G] allele was previously shown to be associated with lower risk of migraine and increased risk of myocardial infarction6–9. Deciphering the mechanisms underlying this pleiotropy might provide important information on the biological underpinnings of these disabling conditions.