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Regular version of the site

Article

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

Nature. 2014.
Debette S., Kamatani Y., Metso T. M., Kloss M., Chauhan G., Engelter S., Pezzini A., Thijs V., Markus H., Dichgans M., Wolf C., Dittrich R., Touzé E., Southerland A. M., Samson Y., Abboud S., Béjot Y., Caso V., Bersano A., Gschwendtner A., Sessa M., Cole J., Lamy C., Medeiros E., Beretta S., Bonati L. H., Grau A., Michel P., Majersik J., Sharma P., Калашникова Л. А., Nazarova M., Добрынина Л. А., Bartels E., Guillon B., van den Herik E., Fernandez-Cadenas I., Jood K., Nalls M., De Leeuw F., Jern C., Cheng Y., Werner I., Metso A., Lichy C., Lyrer P., Brandt T., Boncoraglio G., Wichmann H., Gieger C., Johnson A., Böttcher T., Castellano M., Arveiler D., Ikram M. A., Breteler M., Padovani A., Meschia J., Kuhlenbäumer G., Rolfs A., Worrall B., Ringelstein E., Zelenika D., Tatlisumak T., Lathrop M., Leys D., Amouyel P., Dallongeville J.

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 factors123, and inverse associations with obesity and hypercholesterolemia are described34. No confirmed genetic susceptibility factors have been identified using candidate gene approaches5. We performed genome-wide association studies (GWAS) in 1,393 CeAD cases and 14,416 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 × 10−10), with confirmation in independent follow-up samples (659 CeAD cases and 2,648 controls; P = 3.91 × 10−3; combined P = 1.00 × 10−11). The rs9349379[G] allele was previously shown to be associated with lower risk of migraine and increased risk of myocardial infarction6789. Deciphering the mechanisms underlying this pleiotropy might provide important information on the biological underpinnings of these disabling conditions.