Common variation in PHACTR1 is associated with susceptibility to cervical artery dissection

Debette S., Kamatani Y., Metso T. M. , Kloss M., Chauhan G., Engelter S. T. , ...More

NATURE GENETICS, vol.47, no.1, pp.78-85, 2015 (Journal Indexed in SCI) identifier identifier identifier

  • Publication Type: Article / Article
  • Volume: 47 Issue: 1
  • Publication Date: 2015
  • Doi Number: 10.1038/ng.3154
  • Title of Journal : NATURE GENETICS
  • Page Numbers: pp.78-85


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 2.6/100,000 per year)(1). Minor cervical traumas, infection, migraine and hypertension are putative risk factors(1-3), and inverse associations with obesity and hypercholesterolemia are described(3,4). No confirmed genetic susceptibility factors have been identified using candidate gene approaches(5). We performed genome-wide association studies (GWAS) in 1,393 CeAD cases and 14,416 controls. The rs9349379[G] allele (PHACTR(1)) was associated with lower CeAD risk (odds ratio (OR) = 0.75, 95% confidence interval (CI) = 0.69-0.82; P = 4.46 x 10(-10)), with confirmation in independent follow-up samples (659 CeAD cases and 2,648 controls; P = 3.91 x 10(-3); combined P = 1.00 x 10(-11)). The rs9349379[G] allele was previously shown to be associated with lower risk of migraine and increased risk of myocardial infarction(6-9). Deciphering the mechanisms underlying this pleiotropy might provide important information on the biological underpinnings of these disabling conditions.