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

Stéphanie Debette, Yoichiro Kamatani, Tiina M. Metso, Manja Kloss, Ganesh Chauhan, Stefan T. Engelter, Alessandro Pezzini, Vincent Thijs, Hugh S. Markus, Martin Dichgans, Christiane Wolf, Ralf Dittrich, Emmanuel Touzé, Andrew M. Southerland, Yves Samson, Shérine Abboud, Yannick Béjot, Valeria Caso, Anna Bersano, Andreas GschwendtnerMaria Sessa, John Cole, Chantal Lamy, Elisabeth Medeiros, Simone Beretta, Leo H. Bonati, Armin J. Grau, Patrik Michel, Jennifer J. Majersik, Pankaj Sharma, Ludmila Kalashnikova, Maria Nazarova, Larisa Dobrynina, Eva Bartels, Benoit Guillon, Evita G. Van Den Herik, Israel Fernandez-Cadenas, Katarina Jood, Michael A. Nalls, Frank Erik De Leeuw, Christina Jern, Yu Ching Cheng, Inge Werner, Antti J. Metso, Christoph Lichy, Philippe A. Lyrer, Tobias Brandt, Giorgio B. Boncoraglio, Heinz Erich Wichmann, Christian Gieger, Andrew D. Johnson, Thomas Böttcher, Maurizio Castellano, Dominique Arveiler, M. Arfan Ikram, Monique M B Breteler, Alessandro Padovani, James F Meschia, Gregor Kuhlenbäumer, Arndt Rolfs, Bradford B. Worrall, Erich Bernd Ringelstein, Diana Zelenika, Turgut Tatlisumak, Mark Lathrop, Didier Leys, Philippe Amouyel, Jean Dallongeville

Research output: Contribution to journalArticle

85 Citations (Scopus)

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)<sup>1</sup>. Minor cervical traumas, infection, migraine and hypertension are putative risk factors<sup>1-3</sup>, and inverse associations with obesity and hypercholesterolemia are described<sup>3</sup>,<sup>4</sup>. 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<sup>-10</sup>), with confirmation in independent follow-up samples (659 CeAD cases and 2,648 controls; P = 3.91 × 10<sup>-3</sup>; combined P = 1.00 × 10<sup>-11</sup>). The rs9349379[G] allele was previously shown to be associated with lower risk of migraine and increased risk of myocardial infarction6-9. Deciphering the mechanisms underlying this pleiotropy might provide important information on the.

Original languageEnglish (US)
JournalNature Genetics
Volume47
Issue number1
DOIs
StatePublished - 2014

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Dissection
Arteries
Migraine Disorders
Alleles
Odds Ratio
Vertebral Artery
Genome-Wide Association Study
Genetic Predisposition to Disease
Hypercholesterolemia
Carotid Arteries
Hematoma
Young Adult
Obesity
Stroke
Confidence Intervals
Hypertension
Incidence
Wounds and Injuries
Infection
Population

ASJC Scopus subject areas

  • Genetics

Cite this

Debette, S., Kamatani, Y., Metso, T. M., Kloss, M., Chauhan, G., Engelter, S. T., ... Dallongeville, J. (2014). Common variation in PHACTR1 is associated with susceptibility to cervical artery dissection. Nature Genetics, 47(1). https://doi.org/10.1038/ng.3154

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, Vol. 47, No. 1, 2014.

Research output: Contribution to journalArticle

Debette, S, Kamatani, Y, Metso, TM, Kloss, M, Chauhan, G, Engelter, ST, Pezzini, A, Thijs, V, Markus, HS, Dichgans, M, Wolf, C, Dittrich, R, Touzé, E, Southerland, AM, Samson, Y, Abboud, S, Béjot, Y, Caso, V, Bersano, A, Gschwendtner, A, Sessa, M, Cole, J, Lamy, C, Medeiros, E, Beretta, S, Bonati, LH, Grau, AJ, Michel, P, Majersik, JJ, Sharma, P, Kalashnikova, L, Nazarova, M, Dobrynina, L, Bartels, E, Guillon, B, Van Den Herik, EG, Fernandez-Cadenas, I, Jood, K, Nalls, MA, De Leeuw, FE, Jern, C, Cheng, YC, Werner, I, Metso, AJ, Lichy, C, Lyrer, PA, Brandt, T, Boncoraglio, GB, Wichmann, HE, Gieger, C, Johnson, AD, Böttcher, T, Castellano, M, Arveiler, D, Ikram, MA, Breteler, MMB, Padovani, A, Meschia, JF, Kuhlenbäumer, G, Rolfs, A, Worrall, BB, Ringelstein, EB, Zelenika, D, Tatlisumak, T, Lathrop, M, Leys, D, Amouyel, P & Dallongeville, J 2014, 'Common variation in PHACTR1 is associated with susceptibility to cervical artery dissection', Nature Genetics, vol. 47, no. 1. https://doi.org/10.1038/ng.3154
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. / Common variation in PHACTR1 is associated with susceptibility to cervical artery dissection. In: Nature Genetics. 2014 ; Vol. 47, No. 1.
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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)1. Minor cervical traumas, infection, migraine and hypertension are putative risk factors1-3, and inverse associations with obesity and hypercholesterolemia are described3,4. 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 infarction6-9. Deciphering the mechanisms underlying this pleiotropy might provide important information on the.",
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AU - Debette, Stéphanie

AU - Kamatani, Yoichiro

AU - Metso, Tiina M.

AU - Kloss, Manja

AU - Chauhan, Ganesh

AU - Engelter, Stefan T.

AU - Pezzini, Alessandro

AU - Thijs, Vincent

AU - Markus, Hugh S.

AU - Dichgans, Martin

AU - Wolf, Christiane

AU - Dittrich, Ralf

AU - Touzé, Emmanuel

AU - Southerland, Andrew M.

AU - Samson, Yves

AU - Abboud, Shérine

AU - Béjot, Yannick

AU - Caso, Valeria

AU - Bersano, Anna

AU - Gschwendtner, Andreas

AU - Sessa, Maria

AU - Cole, John

AU - Lamy, Chantal

AU - Medeiros, Elisabeth

AU - Beretta, Simone

AU - Bonati, Leo H.

AU - Grau, Armin J.

AU - Michel, Patrik

AU - Majersik, Jennifer J.

AU - Sharma, Pankaj

AU - Kalashnikova, Ludmila

AU - Nazarova, Maria

AU - Dobrynina, Larisa

AU - Bartels, Eva

AU - Guillon, Benoit

AU - Van Den Herik, Evita G.

AU - Fernandez-Cadenas, Israel

AU - Jood, Katarina

AU - Nalls, Michael A.

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AU - Jern, Christina

AU - Cheng, Yu Ching

AU - Werner, Inge

AU - Metso, Antti J.

AU - Lichy, Christoph

AU - Lyrer, Philippe A.

AU - Brandt, Tobias

AU - Boncoraglio, Giorgio B.

AU - Wichmann, Heinz Erich

AU - Gieger, Christian

AU - Johnson, Andrew D.

AU - Böttcher, Thomas

AU - Castellano, Maurizio

AU - Arveiler, Dominique

AU - Ikram, M. Arfan

AU - Breteler, Monique M B

AU - Padovani, Alessandro

AU - Meschia, James F

AU - Kuhlenbäumer, Gregor

AU - Rolfs, Arndt

AU - Worrall, Bradford B.

AU - Ringelstein, Erich Bernd

AU - Zelenika, Diana

AU - Tatlisumak, Turgut

AU - Lathrop, Mark

AU - Leys, Didier

AU - Amouyel, Philippe

AU - Dallongeville, Jean

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