Common variation in PHACTR1 is associated with susceptibility to cervical artery dissection. |
Authors: |
Debette, Stéphanie Kamatani, Yoichiro Metso, Tiina M Kloss, Manja Chauhan, Ganesh Engelter, Stefan T Pezzini, Alessandro Thijs, Vincent Markus, Hugh S Dichgans, Martin Wolf, Christiane Dittrich, Ralf Touzé, Emmanuel Southerland, Andrew M Samson, Yves Abboud, Shérine Béjot, Yannick Caso, Valeria Bersano, Anna Gschwendtner, Andreas Sessa, Maria Cole, John Lamy, Chantal Medeiros, Elisabeth Beretta, Simone Bonati, Leo H Grau, Armin J Michel, Patrik Majersik, Jennifer J Sharma, Pankaj Kalashnikova, Ludmila Nazarova, Maria Dobrynina, Larisa Bartels, Eva Guillon, Benoit van den Herik, Evita G Fernandez-Cadenas, Israel Jood, Katarina Nalls, Michael A De Leeuw, Frank-Erik Jern, Christina Cheng, Yu-Ching Werner, Inge Metso, Antti J Lichy, Christoph Lyrer, Philippe A Brandt, Tobias Boncoraglio, Giorgio B Wichmann, Heinz-Erich Gieger, Christian Johnson, Andrew D Böttcher, Thomas Castellano, Maurizio Arveiler, Dominique Ikram, M Arfan Breteler, Monique M B Padovani, Alessandro Meschia, James F Kuhlenbäumer, Gregor Rolfs, Arndt Worrall, Bradford B International Stroke Genetics Consortium, Ringelstein, Erich-Bernd Zelenika, Diana Tatlisumak, Turgut Lathrop, Mark Leys, Didier Amouyel, Philippe Dallongeville, Jean CADISP Group,
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Citation: |
Debette S, etal., Nat Genet. 2015 Jan;47(1):78-83. doi: 10.1038/ng.3154. Epub 2014 Nov 24. |
RGD ID: |
401900170 |
Pubmed: |
PMID:25420145 (View Abstract at PubMed) |
PMCID: |
PMC5824623 (View Article at PubMed Central) |
DOI: |
DOI:10.1038/ng.3154 (Journal Full-text) |
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). Minor cervical traumas, infection, migraine and hypertension are putative risk factors, and inverse associations with obesity and hypercholesterolemia are described. No confirmed genetic susceptibility factors have been identified using candidate gene approaches. 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 infarction. Deciphering the mechanisms underlying this pleiotropy might provide important information on the biological underpinnings of these disabling conditions.
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