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.

Common variation in PHACTR1 is associated with susceptibility to cervical artery dissection / 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; Ringelstein, Erich Bernd; Zelenika, Diana; Tatlisumak, Turgut; Lathrop, Mark; Leys, Didier; Amouyel, Philippe; Dallongeville, Jean. - In: NATURE GENETICS. - ISSN 1546-1718. - 47:1(2015), pp. 78-83. [10.1038/ng.3154]

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

PEZZINI, Alessandro;
2015-01-01

Abstract

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.
2015
Common variation in PHACTR1 is associated with susceptibility to cervical artery dissection / 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; Ringelstein, Erich Bernd; Zelenika, Diana; Tatlisumak, Turgut; Lathrop, Mark; Leys, Didier; Amouyel, Philippe; Dallongeville, Jean. - In: NATURE GENETICS. - ISSN 1546-1718. - 47:1(2015), pp. 78-83. [10.1038/ng.3154]
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11381/2964611
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