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 Gschwendtner; Maria 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

doi:10.1038/ng.3154

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

Neurology

Research output: Contribution to journal › Article › peer-review

119 Scopus citations

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 factors^1-3, 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.

Original language	English (US)
Pages (from-to)	78-83
Number of pages	6
Journal	Nature Genetics
Volume	47
Issue number	1
DOIs	https://doi.org/10.1038/ng.3154
State	Published - 2014

ASJC Scopus subject areas

Genetics

Access to Document

10.1038/ng.3154

Cite this

Debette, S., Kamatani, Y., Metso, T. M., Kloss, M., Chauhan, G., Engelter, S. T., Pezzini, A., Thijs, V., Markus, H. S., Dichgans, M., Wolf, C., Dittrich, R., Touzé, E., Southerland, A. M., Samson, Y., Abboud, S., Béjot, Y., Caso, V., Bersano, A., ... Dallongeville, J. (2014). Common variation in PHACTR1 is associated with susceptibility to cervical artery dissection. Nature Genetics, 47(1), 78-83. https://doi.org/10.1038/ng.3154

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, pp. 78-83. https://doi.org/10.1038/ng.3154

@article{c9f2de6266c64fedb5da6d63fa425976,

title = "Common variation in PHACTR1 is associated with susceptibility to cervical artery dissection",

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.",

author = "St{\'e}phanie Debette and Yoichiro Kamatani and Metso, {Tiina M.} and Manja Kloss and Ganesh Chauhan and Engelter, {Stefan T.} and Alessandro Pezzini and Vincent Thijs and Markus, {Hugh S.} and Martin Dichgans and Christiane Wolf and Ralf Dittrich and Emmanuel Touz{\'e} and Southerland, {Andrew M.} and Yves Samson and Sh{\'e}rine Abboud and Yannick B{\'e}jot and Valeria Caso and Anna Bersano and Andreas Gschwendtner and Maria Sessa and John Cole and Chantal Lamy and Elisabeth Medeiros and Simone Beretta and Bonati, {Leo H.} and Grau, {Armin J.} and Patrik Michel and Majersik, {Jennifer J.} and Pankaj Sharma and Ludmila Kalashnikova and Maria Nazarova and Larisa Dobrynina and Eva Bartels and Benoit Guillon and {Van Den Herik}, {Evita G.} and Israel Fernandez-Cadenas and Katarina Jood and Nalls, {Michael A.} and {De Leeuw}, {Frank Erik} and Christina Jern and Cheng, {Yu Ching} and Inge Werner and Metso, {Antti J.} and Christoph Lichy and Lyrer, {Philippe A.} and Tobias Brandt and Boncoraglio, {Giorgio B.} and Wichmann, {Heinz Erich} and Christian Gieger and Johnson, {Andrew D.} and Thomas B{\"o}ttcher and Maurizio Castellano and Dominique Arveiler and Ikram, {M. Arfan} and Breteler, {Monique M.B.} and Alessandro Padovani and Meschia, {James F.} and Gregor Kuhlenb{\"a}umer and Arndt Rolfs and Worrall, {Bradford B.} and Ringelstein, {Erich Bernd} and Diana Zelenika and Turgut Tatlisumak and Mark Lathrop and Didier Leys and Philippe Amouyel and Jean Dallongeville",

year = "2014",

doi = "10.1038/ng.3154",

language = "English (US)",

volume = "47",

pages = "78--83",

journal = "Nature Genetics",

issn = "1061-4036",

publisher = "Nature Publishing Group",

number = "1",

}

TY - JOUR

T1 - Common variation in PHACTR1 is associated with susceptibility to cervical artery dissection

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.

AU - De Leeuw, Frank Erik

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

PY - 2014

Y1 - 2014

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=84928478209&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84928478209&partnerID=8YFLogxK

U2 - 10.1038/ng.3154

DO - 10.1038/ng.3154

M3 - Article

C2 - 25420145

AN - SCOPUS:84928478209

SN - 1061-4036

VL - 47

SP - 78

EP - 83

JO - Nature Genetics

JF - Nature Genetics

IS - 1

ER -

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

Abstract

ASJC Scopus subject areas

Access to Document

Other files and links

Fingerprint

Cite this