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

S Debette, Y Kamatani, TM Metso, M Kloss, G Chauhan, ST Engelter, A Pezzini, V Thijs, HS Markus, M Dichgans, C Wolf, R Dittrich, E Touze, AM Southerland, Y Samson, S Abboud, Y Bejot, V Caso, A Bersano, A GschwendtnerM Sessa, J Cole, C Lamy, E Medeiros, S Beretta, LH Bonati, AJ Grau, P Michel, JJ Majersik, P Sharma, L Kalashnikova, M Nazarova, L Dobrynina, E Bartels, B Guillon, Evita Medici - van den Herik, I Fernandez-Cadenas, K Jood, MA Nalls, FE Leeuw, C Jern, YC Cheng, I Werner, AJ Metso, C Lichy, PA Lyrer, T Brandt, GB Boncoraglio, HE Wichmann, C Gieger, AD Johnson, T Bottcher, M Castellano, D Arveiler, Arfan Ikram, Monique Breteler, A Padovani, JF Meschia, G Kuhlenbaumer, A Rolfs, BB Worrall, EB Ringelstein, D Zelenika, T Tatlisumak, M Lathrop, D Leys, P Amouyel, J Dallongeville

Research output: Contribution to journalArticleAcademicpeer-review

179 Citations (Scopus)


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.
Original languageUndefined/Unknown
Pages (from-to)78-83
Number of pages6
JournalNature Genetics
Issue number1
Publication statusPublished - 2015

Research programs

  • EMC COEUR-09
  • EMC NIHES-01-64-01
  • EMC NIHES-03-30-02

Cite this