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118 results on '"Marti-Fabregas, Joan"'

1. Multi-ancestry GWAS reveals excitotoxicity associated with outcome after ischaemic stroke

Author

Ibanez, Laura, Heitsch, Laura, Carrera, Caty, Farias, Fabiana HG, Del Aguila, Jorge L, Dhar, Rajat, Budde, John, Bergmann, Kristy, Bradley, Joseph, Harari, Oscar, Phuah, Chia Ling, Lemmens, Robin, Viana Oliveira Souza, Alessandro A, Moniche, Francisco, Cabezas-Juan, Antonio, Arenillas, Juan Francisco, Krupinksi, Jerzy, Cullell, Natalia, Torres-Aguila, Nuria, Muiño, Elena, Cárcel-Márquez, Jara, Marti-Fabregas, Joan, Delgado-Mederos, Raquel, Marin-Bueno, Rebeca, Hornick, Alejandro, Vives-Bauza, Cristofol, Navarro, Rosa Diaz, Tur, Silvia, Jimenez, Carmen, Obach, Victor, Segura, Tomas, Serrano-Heras, Gemma, Chung, Jong Won, Roquer, Jaume, Soriano-Tarraga, Carol, Giralt-Steinhauer, Eva, Mola-Caminal, Marina, Pera, Joanna, Lapicka-Bodzioch, Katarzyna, Derbisz, Justyna, Davalos, Antoni, Lopez-Cancio, Elena, Muñoz, Lucia, Tatlisumak, Turgut, Molina, Carlos, Ribo, Marc, Bustamante, Alejandro, Sobrino, Tomas, Castillo-Sanchez, Jose, Campos, Francisco, Rodriguez-Castro, Emilio, Arias-Rivas, Susana, Rodríguez-Yáñez, Manuel, Herbosa, Christina, Ford, Andria L, Gutierrez-Romero, Alonso, Uribe-Pacheco, Rodrigo, Arauz, Antonio, Lopes-Cendes, Iscia, Lowenkopf, Theodore, Barboza, Miguel A, Amini, Hajar, Stamova, Boryana, Ander, Bradley P, Sharp, Frank R, Kim, Gyeong Moon, Bang, Oh Young, Jimenez-Conde, Jordi, Slowik, Agnieszka, Stribian, Daniel, Tsai, Ellen A, Burkly, Linda C, Montaner, Joan, Fernandez-Cadenas, Israel, Lee, Jin Moo, and Cruchaga, Carlos

Subjects
Epidemiology, Health Sciences, Neurosciences, Human Genome, Genetics, Stroke, Biotechnology, Aging, Brain Disorders, Cerebrovascular, 2.1 Biological and endogenous factors, Neurological, Bayes Theorem, Brain Ischemia, Genome-Wide Association Study, Humans, Ischemic Stroke, United States, ischaemic stroke, neuroprotection, genetics, NIHSS, Medical and Health Sciences, Psychology and Cognitive Sciences, Neurology & Neurosurgery, Biomedical and clinical sciences, Health sciences, Psychology
Abstract

During the first hours after stroke onset, neurological deficits can be highly unstable: some patients rapidly improve, while others deteriorate. This early neurological instability has a major impact on long-term outcome. Here, we aimed to determine the genetic architecture of early neurological instability measured by the difference between the National Institutes of Health Stroke Scale (NIHSS) within 6 h of stroke onset and NIHSS at 24 h. A total of 5876 individuals from seven countries (Spain, Finland, Poland, USA, Costa Rica, Mexico and Korea) were studied using a multi-ancestry meta-analyses. We found that 8.7% of NIHSS at 24 h of variance was explained by common genetic variations, and also that early neurological instability has a different genetic architecture from that of stroke risk. Eight loci (1p21.1, 1q42.2, 2p25.1, 2q31.2, 2q33.3, 5q33.2, 7p21.2 and 13q31.1) were genome-wide significant and explained 1.8% of the variability suggesting that additional variants influence early change in neurological deficits. We used functional genomics and bioinformatic annotation to identify the genes driving the association from each locus. Expression quantitative trait loci mapping and summary data-based Mendelian randomization indicate that ADAM23 (log Bayes factor = 5.41) was driving the association for 2q33.3. Gene-based analyses suggested that GRIA1 (log Bayes factor = 5.19), which is predominantly expressed in the brain, is the gene driving the association for the 5q33.2 locus. These analyses also nominated GNPAT (log Bayes factor = 7.64) ABCB5 (log Bayes factor = 5.97) for the 1p21.1 and 7p21.1 loci. Human brain single-nuclei RNA-sequencing indicates that the gene expression of ADAM23 and GRIA1 is enriched in neurons. ADAM23, a presynaptic protein and GRIA1, a protein subunit of the AMPA receptor, are part of a synaptic protein complex that modulates neuronal excitability. These data provide the first genetic evidence in humans that excitotoxicity may contribute to early neurological instability after acute ischaemic stroke.

Published
2022

2. A multitrait genetic study of hemostatic factors and hemorrhagic transformation after stroke treatment

Author

Dehghan, Abbas, Heath, Adam S., Morrison, Alanna C., Reiner, Alex P., Johnson, Andrew, Richmond, Anne, Peters, Annette, van Hylckama Vlieg, Astrid, McKnight, Barbara, Psaty, Bruce M., Hayward, Caroline, Ward-Caviness, Cavin, O’Donnell, Christopher, Chasman, Daniel, Strachan, David P., Tregouet, David A., Mook-Kanamori, Dennis, Gill, Dipender, Thibord, Florian, Asselbergs, Folkert W., Leebeek, Frank W.G., Rosendaal, Frits R., Davies, Gail, Homuth, Georg, Temprano, Gerard, Campbell, Harry, Taylor, Herman A., Bressler, Jan, Huffman, Jennifer E., Rotter, Jerome I., Yao, Jie, Wilson, James F., Bis, Joshua C., Hahn, Julie M., Desch, Karl C., Wiggins, Kerri L., Díez-Ahijado, Laia, Raffield, Laura M., Bielak, Lawrence F., Yanek, Lisa R., Kleber, Marcus E., Sabater-Lleal, Maria, Mueller, Martina, Kavousi, Maryam, Mangino, Massimo, Conomos, Matthew P., Liu, Melissa, Brown, Michael R., Jhun, Min-A, Chen, Ming-Huei, de Maat, Moniek P.M., Pankratz, Nathan, Smith, Nicholas L., Peyser, Patricia A., Elliot, Paul, de Vries, Paul S., Wei, Peng, Wild, Philipp S., Morange, Pierre E., van der Harst, Pim, Yang, Qiong, Marioni, Riccardo, Li, Ruifang, Damrauer, Scott M., Cox, Simon R., Trompet, Stella, Felix, Stephan B., Völker, Uwe, Tang, Weihong, Koenig, Wolfgang, Jukema, J. Wouter, Guo, Xiuqing, Gallego-Fabrega, Cristina, Temprano-Sagrera, Gerard, Cárcel-Márquez, Jara, Muiño, Elena, Cullell, Natalia, Lledós, Miquel, Llucià-Carol, Laia, Martin-Campos, Jesús M., Sobrino, Tomás, Castillo, José, Millán, Mònica, Muñoz-Narbona, Lucía, López-Cancio, Elena, Ribó, Marc, Alvarez-Sabin, Jose, Jiménez-Conde, Jordi, Roquer, Jaume, Tur, Silvia, Obach, Victor, Arenillas, Juan F., Segura, Tomas, Serrano-Heras, Gemma, Marti-Fabregas, Joan, Freijo-Guerrero, Marimar, Moniche, Francisco, Castellanos, Maria del Mar, and Fernández-Cadenas, Israel

Published
2024
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5. Frequency, Predictors, Etiology, and Outcomes for Deep Intracerebral Hemorrhage without Hypertension

Author

Prats-Sánchez, Luis, Iruzubieta, Pablo, Vesperinas, Ana, Collet, Roger, Martínez-Domeño, Alejandro, Guisado-Alonso, Daniel, Camps-Renom, Pol, Delgado-Mederos, Raquel, Guasch-Jiménez, Marina, Ramos-Pachón, Anna, Rodríguez-Antigüedad, Jon, Campo-Caballero, David, Equiza, Jon, de la Riva, Patricia, Martínez-Zabaleta, Maite, de Arce, Ana, and Martí-Fàbregas, Joan

Published
2022
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6. The Role of Vascular Imaging atReferral Centers in the Drip and Ship Paradigm

Author

Flores, Alan, Seró, Laia, Gomez-Choco, Manuel, Ustrell, Xavier, Pellisé, Anna, Viñas, Jaume, Rodriguez, Paula, Monterde, Angela, Castilho, Gislaine, Rubiera, Marta, Amaro, Sergi, Padrós, Maria Angels Font, Cardona, Pedro, Marti-Fabregas, Joan, Molina, Carlos A., Serena, Joaquín, Jimenez-Fábrega, Francesc Xavier, Purroy, Francisco, Zaragoza-Brunet, José, Cocho, Dolores, Palomeras, Ernest, Kuprinski, Jurek, Más, Natalia, Hernández-Perez, Maria, Sanjurjo, Eduard, Carrión, Dolors, Costa, Xavier, Barceló, Miquel, Monedero, Jordi, Catena, Esther, Rybyeba, Maria, Díaz, Gloria, de la Ossa, Natalia Perez, and Ribó, Marc

Published
2022
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9. Development of imaging-based risk scores for prediction of intracranial haemorrhage and ischaemic stroke in patients taking antithrombotic therapy after ischaemic stroke or transient ischaemic attack: a pooled analysis of individual patient data from cohort studies

Author

Harkness, Kirsty, Shaw, Louise, Sword, Jane, Mohd Nor, Azlisham, Sharma, Pankaj, Kelly, Deborah, Harrington, Frances, Randall, Marc, Smith, Matthew, Mahawish, Karim, Elmarim, Abduelbaset, Esisi, Bernard, Cullen, Claire, Nallasivam, Arumug, Price, Christopher, Barry, Adrian, Roffe, Christine, Coyle, John, Hassan, Ahamad, Birns, Jonathan, Cohen, David, Sekaran, Lakshmanan, Parry-Jones, Adrian, Parry, Anthea, Hargroves, David, Proschel, Harald, Datta, Prabel, Darawil, Khaled, Manoj, Aravindakshan, Burn, Mathew, Patterson, Chris, Giallombardo, Elio, Smyth, Nigel, Mansoor, Syed, Anwar, Ijaz, Marsh, Rachel, Ispoglou, Sissi, Chadha, Dinesh, Prabhakaran, Mathuri, Meenakishundaram, Sanjeevikumar, O'Connell, Janice, Scott, Jon, Krishnamurthy, Vinodh, Aghoram, Prasanna, McCormick, Michael, Sprigg, Nikola, O'Mahony, Paul, Cooper, Martin, Choy, Lillian, Wilkinson, Peter, Leach, Simon, Caine, Sarah, Burger, Ilse, Gunathilagan, Gunaratam, Guyler, Paul, Emsley, Hedley, Davis, Michelle, Manawadu, Dulka, Pasco, Kath, Mamun, Maam, Luder, Robert, Sajid, Mahmud, Okwera, James, Warburton, Elizabeth, Saastamoinen, Kari, England, Timothy, Putterill, Janet, Flossman, Enrico, Power, Michael, Dani, Krishna, Mangion, David, Suman, Appu, Corrigan, John, Lawrence, Enas, Vahidassr, Djamil, Shakeshaft, Clare, Brown, Martin, Charidimou, Andreas, Cohen, Hannah, Banerjee, Gargi, Houlden, Henry, White, Mark, Yousry, Tarek, Flossmann, Enrico, Muir, Keith, Gratz, Pascal, Mattle, Heinrich, Panos, Leonidas, Korczyn, Amos, Kliper, Efrat, Maeder, Philippe, Gass, Achim, Pachai, Chahin, Bracoub, Luc, Douste-Blazy, Marie-Yvonne, Fratacci, Marie Dominique, Vicaut, Eric, Sato, Shoichiro, Miwa, Kaori, Fujita, Kyohei, Ide, Toshihiro, Ma, Henry, Ly, John, Singhal, Shaloo, Chandra, Ronil, Slater, Lee-Anne, Soufan, Cathy, Moran, Christopher, Traenka, Christopher, Thilemann, Sebastian, Fladt, Joachim, Gensicke, Henrik, Bonati, Leo, Kim, Beom Joon, Han, Moon-Ku, Kang, Jihoon, Ko, Eunbin, Yang, Mi Hwa, Jang, Myung Suk, Murphy, Sean, Carty, Fiona, Akijian, Layan, Thornton, John, Schembri, Mark, Douven, Elles, Delgado-Mederos, Raquel, Marín, Rebeca, Camps-Renom, Pol, Guisado-Alonso, Daniel, Nuñez, Fidel, Medrano-Martorell, Santiago, Merino, Elisa, Iida, Kotaro, Ikeda, Syuhei, Irie, Hiroyuki, Demirelli, Derya Selcuk, Medanta, Jayesh Modi, Zerna, Charlotte, Hernández, Maria Valdés, Armitage, Paul, Heye, Anna, Muñoz-Maniega, Susana, Sakka, Eleni, Thrippleton, Michael, Dennis, Martin, Beigneux, Ysoline, Silva, Mauro, Venketasubramanian, Narayanaswamy, Ho, Shu Leung, Cheung, Raymond Tak Fai, Chan, Koon Ho, Teo, Kay Cheong, Hui, Edward, Kwan, Joseph Shiu Kwong, Chang, Richard, Tse, Man Yu, Hoi, Chu Peng, Chan, Chung Yan, Chan, Oi Ling, Cheung, Ryan Hoi Kit, Wong, Edmund Ka Ming, Leung, Kam Tat, Tsang, Suk Fung, Ip, Hing Lung, Ma, Sze Ho, Ma, Karen, Fong, Wing Chi, Li, Siu Hung, Li, Richard, Ng, Ping Wing, Wong, Kwok Kui, Liu, Wenyan, Wong, Lawrence, Ramos, Lino, De Schryver, Els, Jöbsis, Joost, van der Sande, Jaap, Brouwers, Paul, Roos, Yvo, Stam, Jan, Bakker, Stef, Verbiest, Henk, Schoonewille, Wouter, Linn, Cisca, Hertzberger, Leopold, van Gemert, Maarten, Berntsen, Paul, Van Dam-Nolen, Dianne, Kooi, M Eline, Van der Lugt, Aad, Koudstaal, Peter, Leff, Alexander, Ward, Nicholas, Nachev, Parashkev, Perry, Richard, Ozkan, Hatice, Mitchell, John, Best, Jonathan G, Ambler, Gareth, Wilson, Duncan, Lee, Keon-Joo, Lim, Jae-Sung, Shiozawa, Masayuki, Koga, Masatoshi, Li, Linxin, Lovelock, Caroline, Chabriat, Hugues, Hennerici, Michael, Wong, Yuen Kwun, Mak, Henry Ka Fung, Prats-Sanchez, Luis, Martínez-Domeño, Alejandro, Inamura, Shigeru, Yoshifuji, Kazuhisa, Arsava, Ethem Murat, Horstmann, Solveig, Purrucker, Jan, Lam, Bonnie Yin Ka, Wong, Adrian, Kim, Young Dae, Song, Tae-Jin, Lemmens, Robin, Eppinger, Sebastian, Gattringer, Thomas, Uysal, Ender, Tanriverdi, Zeynep, Bornstein, Natan M, Ben Assayag, Einor, Hallevi, Hen, Molad, Jeremy, Nishihara, Masashi, Tanaka, Jun, Coutts, Shelagh B, Polymeris, Alexandros, Wagner, Benjamin, Seiffge, David J, Lyrer, Philippe, Algra, Ale, Kappelle, L Jaap, Al-Shahi Salman, Rustam, Jäger, Hans R, Lip, Gregory Y H, Fischer, Urs, El-Koussy, Marwan, Mas, Jean-Louis, Legrand, Laurence, Karayiannis, Christopher, Phan, Thanh, Gunkel, Sarah, Christ, Nicolas, Abrigo, Jill, Leung, Thomas, Chu, Winnie, Chappell, Francesca, Makin, Stephen, Hayden, Derek, Williams, David J, Mess, Werner H, Nederkoorn, Paul J, Barbato, Carmen, Browning, Simone, Wiegertjes, Kim, Tuladhar, Anil M, Maaijwee, Noortje, Guevarra, Anne Cristine, Yatawara, Chathuri, Mendyk, Anne-Marie, Delmaire, Christine, Köhler, Sebastian, van Oostenbrugge, Robert, Zhou, Ying, Xu, Chao, Hilal, Saima, Gyanwali, Bibek, Chen, Christopher, Lou, Min, Staals, Julie, Bordet, Régis, Kandiah, Nagaendran, de Leeuw, Frank-Erik, Simister, Robert, Hendrikse, Jeroen, Kelly, Peter J, Wardlaw, Joanna, Soo, Yannie, Fluri, Felix, Srikanth, Velandai, Calvet, David, Jung, Simon, Kwa, Vincent I H, Engelter, Stefan T, Peters, Nils, Smith, Eric E, Hara, Hideo, Yakushiji, Yusuke, Orken, Dilek Necioglu, Fazekas, Franz, Thijs, Vincent, Heo, Ji Hoe, Mok, Vincent, Veltkamp, Roland, Ay, Hakan, Imaizumi, Toshio, Gomez-Anson, Beatriz, Lau, Kui Kai, Jouvent, Eric, Rothwell, Peter M, Toyoda, Kazunori, Bae, Hee-Joon, Marti-Fabregas, Joan, and Werring, David J

Published
2021
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10. A multitrait genetic study of hemostatic factors and hemorrhagic transformation after stroke treatment

Author

National Heart, Lung, and Blood Institute (US), Generalitat de Catalunya, Instituto de Salud Carlos III, European Commission, Gallego-Fabrega, Cristina, Temprano-Sagrera, Gerard, Cárcel-Márquez, Jara, Muiño, Elena, Cullell, Natalia, Lledós, Miquel, Llucià-Carol, Laia, Martin-Campos, Jesús M, Sobrino, Tomás, Castillo, José, Millán, Mònica, Muñoz-Narbona, Lucía, López-Cancio, Elena, Ribó, Marc, Álvarez-Sabín, José, Jiménez-Conde, Jordi, Roquer, Jaume, Tur, Silvia, Obach, Victor, Arenillas, Juan F., Segura, Tomás, Serrano-Heras, Gemma, Marti-Fabregas, Joan, Freijo-Guerrero, Marimar, Moniche, Francisco, Castellanos, Maria Del Mar, Morrison, Alanna C., Smith, Nicholas L., de Vries, Paul S., Fernández-Cadenas, Israel, Sabater-Lleal, Maria, National Heart, Lung, and Blood Institute (US), Generalitat de Catalunya, Instituto de Salud Carlos III, European Commission, Gallego-Fabrega, Cristina, Temprano-Sagrera, Gerard, Cárcel-Márquez, Jara, Muiño, Elena, Cullell, Natalia, Lledós, Miquel, Llucià-Carol, Laia, Martin-Campos, Jesús M, Sobrino, Tomás, Castillo, José, Millán, Mònica, Muñoz-Narbona, Lucía, López-Cancio, Elena, Ribó, Marc, Álvarez-Sabín, José, Jiménez-Conde, Jordi, Roquer, Jaume, Tur, Silvia, Obach, Victor, Arenillas, Juan F., Segura, Tomás, Serrano-Heras, Gemma, Marti-Fabregas, Joan, Freijo-Guerrero, Marimar, Moniche, Francisco, Castellanos, Maria Del Mar, Morrison, Alanna C., Smith, Nicholas L., de Vries, Paul S., Fernández-Cadenas, Israel, and Sabater-Lleal, Maria

Abstract

[Background] Thrombolytic recombinant tissue plasminogen activator (r-tPA) treatment is the only pharmacologic intervention available in the ischemic stroke acute phase. This treatment is associated with an increased risk of intracerebral hemorrhages, known as hemorrhagic transformations (HTs), which worsen the patient’s prognosis., [Objectives] To investigate the association between genetically determined natural hemostatic factors’ levels and increased risk of HT after r-tPA treatment., [Methods] Using data from genome-wide association studies on the risk of HT after r-tPA treatment and data on 7 hemostatic factors (factor [F]VII, FVIII, von Willebrand factor [VWF], FXI, fibrinogen, plasminogen activator inhibitor-1, and tissue plasminogen activator), we performed local and global genetic correlation estimation multitrait analyses and colocalization and 2-sample Mendelian randomization analyses between hemostatic factors and HT., [Results] Local correlations identified a genomic region on chromosome 16 with shared covariance: fibrinogen-HT, P = 2.45 × 10−11. Multitrait analysis between fibrinogen-HT revealed 3 loci that simultaneously regulate circulating levels of fibrinogen and risk of HT: rs56026866 (PLXND1), P = 8.80 × 10−10; rs1421067 (CHD9), P = 1.81 × 10−14; and rs34780449, near ROBO1 gene, P = 1.64 × 10−8. Multitrait analysis between VWF-HT showed a novel common association regulating VWF and risk of HT after r-tPA at rs10942300 (ZNF366), P = 1.81 × 10−14. Mendelian randomization analysis did not find significant causal associations, although a nominal association was observed for FXI-HT (inverse-variance weighted estimate [SE], 0.07 [−0.29 to 0.00]; odds ratio, 0.87; 95% CI, 0.75-1.00; raw P = .05)., [Conclusion] We identified 4 shared loci between hemostatic factors and HT after r-tPA treatment, suggesting common regulatory mechanisms between fibrinogen and VWF levels and HT. Further research to determine a possible mediating effect of fibrinogen on HT risk is needed.

Published
2024

11. Influence of Hospital Type on Outcomes of Patients With Acute Spontaneous Intracerebral Hemorrhage: A Population-Based Study.

Author

Marti-Fabregas, Joan, Ramos-Pachón, Anna, Prats-Sanchez, Luis, Núñez-Guillén, Ana, Rodríguez, Blanca Lara, Rodriguez-Luna, David, Amaro, Sergio, Silva, Yolanda, Rodriguez-Campello, Ana, Puig, Isabel, Gomez-Choco, Manuel, Vázquez-Justes, Daniel, Guanyabens, Nicolau, Cocho, Dolores, Cánovas, David, Steinhauer, Eva Giralt, Llull, Laura, Guasch-Jiménez, Marina, Martinez-Domeño, Alejandro, and Marin, Rebeca

Published
2024
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13. Cerebral microbleeds and stroke risk after ischaemic stroke or transient ischaemic attack: a pooled analysis of individual patient data from cohort studies

Author

Harkness, Kirsty, Shaw, Louise, Sword, Jane, Mohd Nor, Azlisham, Sharma, Pankaj, Kelly, Deborah, Harrington, Frances, Randall, Marc, Smith, Matthew, Mahawish, Karim, Elmarim, Abduelbaset, Esisi, Bernard, Cullen, Claire, Nallasivam, Arumug, Price, Christopher, Barry, Adrian, Roffe, Christine, Coyle, John, Hassan, Ahamad, Birns, Jonathan, Cohen, David, Sekaran, Lakshmanan, Parry-Jones, Adrian, Parry, Anthea, Hargroves, David, Proschel, Harald, Datta, Prabel, Darawil, Khaled, Manoj, Aravindakshan, Burn, Mathew, Patterson, Chris, Giallombardo, Elio, Smyth, Nigel, Mansoor, Syed, Anwar, Ijaz, Marsh, Rachel, Ispoglou, Sissi, Chadha, Dinesh, Prabhakaran, Mathuri, Meenakishundaram, Sanjeevikumar, O'Connell, Janice, Scott, Jon, Krishnamurthy, Vinodh, Aghoram, Prasanna, McCormick, Michael, Sprigg, Nikola, O'Mahony, Paul, Cooper, Martin, Choy, Lillian, Wilkinson, Peter, Leach, Simon, Caine, Sarah, Burger, Ilse, Gunathilagan, Gunaratam, Guyler, Paul, Emsley, Hedley, Davis, Michelle, Manawadu, Dulka, Pasco, Kath, Mamun, Maam, Luder, Robert, Sajid, Mahmud, Okwera, James, Warburton, Elizabeth, Saastamoinen, Kari, England, Timothy, Putterill, Janet, Flossman, Enrico, Power, Michael, Dani, Krishna, Mangion, David, Suman, Appu, Corrigan, John, Lawrence, Enas, Vahidassr, Djamil, Shakeshaft, Clare, Brown, Martin, Charidimou, Andreas, Cohen, Hannah, Banerjee, Gargi, Houlden, Henry, White, Mark, Yousry, Tarek, Flossmann, Enrico, Muir, Keith, El-Koussy, Marwan, Gratz, Pascal, Molad, Jeremy, Korczyn, Amos, Kliper, Efrat, Maeder, Philippe, Gass, Achim, Pachai, Chahin, Bracoub, Luc, Douste-Blazy, Marie-Yvonne, Fratacci, Marie Dominique, Vicaut, Eric, Sato, Shoichiro, Miwa, Kaori, Fujita, Kyohei, Ide, Toshihiro, Ma, Henry, Ly, John, Singhal, Shahoo, Chandra, Ronil, Slater, Lee-Anne, Soufan, Cathy, Moran, Christopher, Traenka, Christopher, Thilemann, Sebastian, Fladt, Joachim, Gensicke, Henrik, Bonati, Leo, Kim, Beom Joon, Han, Moon-Ku, Kang, Jihoon, Ko, Eunbin, Yang, Mi Hwa, Jang, Myung Suk, Murphy, Sean, Carty, Fiona, Akijian, Layan, Thornton, John, Schembri, Mark, Douven, Elles, Delgado-Mederos;, Raquel, Marín, Rebeca, Camps-Renom, Pol, Guisado-Alonso, Daniel, Nuñez, Fidel, Medrano-Martorell, Santiago, Merino, Elisa, Iida, Kotaro, Ikeda, Syuhei, Nishihara, Masashi, Irie, Hiroyuki, Demirelli, Derya Selcuk, Medanta, Jayesh Modi, Zerna, Charlotte, Hernández, Maria Valdés, Armitage, Paul, Heye, Anna, Muñoz-Maniega, Susana, Sakka, Eleni, Thrippleton, Michael, Dennis, Martin, Beigneux, Ysoline, Silva, Mauro, Venketasubramanian, Narayanaswamy, Ho, Shu Leung, Cheung, Raymond Tak Fai, Chan, Koon Ho, Teo, Kay Cheong, Hui, Edward, Kwan, Joseph Shiu Kwong, Chang, Richard, Tse, Man Yu, Hoi, Chu Peng, Chan, Chung Yan, Chan, Oi Ling, Cheung, Ryan Hoi Kit, Wong, Edmund Ka Ming, Leung, Kam Tat, Tsang, Suk Fung, Ip, Hing Lung, Ma, Sze Ho, Ma, Karen, Fong, Wing Chi, Li, Siu Hung, Li, Richard, Ng, Ping Wing, Wong, Kwok Kui, Liu, Wenyan, Wong, Lawrence, Ramos, Lino, De Schryver, Els, Jöbsis, Joost, van der Sande, Jaap, Brouwers, Paul, Roos, Yvo, Stam, Jan, Bakker, Stef, Verbiest, Henk, Schoonewille, Wouter, Linn, Cisca, Hertzberger, Leopold, van Gemert, Maarten, Berntsen, Paul, Hendrikse, Jeroen, Nederkoorn, Paul, Mess, Werner, Koudstaal, Peter, Leff, Alexander, Ward, Nicholas, Nachev, Parashkev, Perry, Richard, Ozkan, Hatice, Mitchell, John, Wilson, Duncan, Ambler, Gareth, Lee, Keon-Joo, Lim, Jae-Sung, Shiozawa, Masayuki, Koga, Masatoshi, Li, Linxin, Lovelock, Caroline, Chabriat, Hugues, Hennerici, Michael, Wong, Yuen Kwun, Mak, Henry Ka Fung, Prats-Sánchez, Luis, Martínez-Domeño, Alejandro, Inamura, Shigeru, Yoshifuji, Kazuhisa, Arsava, Ethem Murat, Horstmann, Solveig, Purrucker, Jan, Lam, Bonnie Yin Ka, Wong, Adrian, Kim, Young Dae, Song, Tae-Jin, Schrooten, Maarten, Lemmens, Robin, Eppinger, Sebastian, Gattringer, Thomas, Uysal, Ender, Tanriverdi, Zeynep, Bornstein, Natan M, Assayag, Einor Ben, Hallevi, Hen, Tanaka, Jun, Hara, Hideo, Coutts, Shelagh B, Hert, Lisa, Polymeris, Alexandros, Seiffge, David J, Lyrer, Philippe, Algra, Ale, Kappelle, Jaap, Al-Shahi Salman, Rustam, Jäger, Hans R, Lip, Gregory Y H, Mattle, Heinrich P, Panos, Leonidas D, Mas, Jean-Louis, Legrand, Laurence, Karayiannis, Christopher, Phan, Thanh, Gunkel, Sarah, Christ, Nicolas, Abrigo, Jill, Leung, Thomas, Chu, Winnie, Chappell, Francesca, Makin, Stephen, Hayden, Derek, Williams, David J, Kooi, M Eline, van Dam-Nolen, Dianne H K, Barbato, Carmen, Browning, Simone, Wiegertjes, Kim, Tuladhar, Anil M, Maaijwee, Noortje, Guevarra, Christine, Yatawara, Chathuri, Mendyk, Anne-Marie, Delmaire, Christine, Köhler, Sebastian, van Oostenbrugge, Robert, Zhou, Ying, Xu, Chao, Hilal, Saima, Gyanwali, Bibek, Chen, Christopher, Lou, Min, Staals, Julie, Bordet, Régis, Kandiah, Nagaendran, de Leeuw, Frank-Erik, Simister, Robert, van der Lugt, Aad, Kelly, Peter J, Wardlaw, Joanna M, Soo, Yannie, Fluri, Felix, Srikanth, Velandai, Calvet, David, Jung, Simon, Kwa, Vincent I H, Engelter, Stefan T, Peters, Nils, Smith, Eric E, Yakushiji, Yusuke, Orken, Dilek Necioglu, Fazekas, Franz, Thijs, Vincent, Heo, Ji Hoe, Mok, Vincent, Veltkamp, Roland, Ay, Hakan, Imaizumi, Toshio, Gomez-Anson, Beatriz, Lau, Kui Kai, Jouvent, Eric, Rothwell, Peter M, Toyoda, Kazunori, Bae, Hee-Joon, Marti-Fabregas, Joan, and Werring, David J

Published
2019
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14. Absolute risk and predictors of the growth of acute spontaneous intracerebral haemorrhage: a systematic review and meta-analysis of individual patient data

Author

Hanley, Daniel F, Jr, Butcher, Kenneth S, Davis, Stephen, Gregson, Barbara, Lees, Kennedy R, Lyden, Patrick D, Mayer, Stephan A, Muir, Keith W, Steiner, Thorsten, Xie, Peng, Bakhshayesh, Babak, McDonald, Mark, Brott, Thomas, Pennati, Paolo, Parry-Jones, Adrian R, Smith, Craig J, Hopkins, Stephen J, Slevin, Mark, Campi, Veronica, Singh, Puneetpal, Papa, Francesca, Popa-Wagner, Aurel, Tudorica, Valeria, Takagi, Ryo, Teramoto, Akira, Weissenborn, Karin, Lanfermann, Heinrich, Al-Shahi Salman, Rustam, Frantzias, Joseph, Lee, Robert J, Battey, Thomas W K, Ayres, Alison M, Goldstein, Joshua N, Wang, Xia, Arima, Hisatomi, Hasegawa, Hitoshi, Oishi, Makoto, Godoy, Daniel A, Masotti, Luca, Dowlatshahi, Dar, Rodriguez-Luna, David, Molina, Carlos A, Jang, Dong-Kyu, Davalos, Antonio, Castillo, José, Yao, Xiaoying, Claassen, Jan, Volbers, Bastian, Kazui, Seiji, Okada, Yasushi, Fujimoto, Shigeru, Toyoda, Kazunori, Li, Qi, Khoury, Jane, Delgado, Pilar, Sabín, José Álvarez, Hernández-Guillamon, Mar, Prats-Sánchez, Luis, Cai, Chunyan, Kate, Mahesh P, McCourt, Rebecca, Venkatasubramanian, Chitra, Diringer, Michael N, Ikeda, Yukio, Worthmann, Hans, Ziai, Wendy C, d'Esterre, Christopher D, Aviv, Richard I, Raab, Peter, Murai, Yasuo, Zazulia, Allyson R, Seyedsaadat, Seyed Mohammad, Grotta, James C, Martí-Fàbregas, Joan, Montaner, Joan, Broderick, Joseph, Yamamoto, Haruko, Staykov, Dimitre, Connolly, E Sander, Selim, Magdy, Leira, Rogelio, Moon, Byung Hoo, Demchuk, Andrew M, Di Napoli, Mario, Fujii, Yukihiko, Anderson, Craig S, and Rosand, Jonathan

Published
2018
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16. Recommendations for Clinical Trials in ICH: The Second Hemorrhagic Stroke Academia Industry Roundtable

Author

Selim, Magdy, Hanley, Daniel, Steiner, Thorsten, Christensen, Hanne Krarup, Lafuente, Jesus, Rodriguez, David, Selim, Magdy, Keep, Richard, Steiner, Thorsten, Anderson, Craig, Hanley, Daniel, Keep, Richard, Parry-Jones, Adrian, Nilsson, Michael, Sunnerhagen, Katharina Stibrant, Novick, Elizabeth, Aronowski, Jaroslaw, Lawson, Brooke, Chaudhary, Neeraj, Zhou-Ping, Tang, Steiner, Thorsten, Christensen, Hanne Krarup, Zuccarello, Mario, Woo, Daniel, Shoamanesh, Ashkan, Qureshi, Adnan I., Cordonnier, Charlotte, Anderson, Craig, Klijn, Karin, Salman, Rustam Al-Shahi, Sprigg, Nikola, Gregson, Barbara, Mendelow, David, Gaudin, Christophe, Pandey, Aditya, Ziai, Wendy, Alcázar-Romero, Pedro Pablo, Montaner, Joan, Marti-Fabregas, Joan, Nilsson, Sara, Schenk, Bettina, Riess, Hanno, You, Chao, Gaist, David, and Broderick, Joseph

Published
2020
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17. Efficacy and Safety of Rivaroxaban Versus Aspirin in Embolic Stroke of Undetermined Source and Carotid Atherosclerosis

Author

Ntaios, George, Swaminathan, Balakumar, Berkowitz, Scott D., Gagliardi, Rubens José, Lang, Wilfried, Siegler, James E., Lavados, Pablo, Mundl, Hardi, Bornstein, Natan, Meseguer, Elena, Amarenco, Pierre, Cucchiara, Brett, Camps-Renom, Pol, Makaritsis, Konstantinos, Korompoki, Eleni, Papavasileiou, Vasileios, Marti-Fabregas, Joan, Milionis, Haralampos, Vemmos, Konstantinos, Connolly, Stuart J., and Hart, Robert G.

Published
2019
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19. Genetic Architecture of Ischaemic Strokes after COVID-19 Shows Similarities with Large Vessel Strokes

Author

CSIC - Plataforma Temática Interdisciplinar del CSIC Salud Global (PTI Salud Global), European Commission, Instituto de Salud Carlos III, Generalitat de Catalunya, National Fund for Scientific Research (Belgium), Fonds Léon Fredericq, Llucià-Carol, Laia, Muiño, Elena, Cullell, Nàtalia, Cárcel-Márquez, Jara, Lledós, Miquel, Gallego-Fabrega, Cristina, Martín-Campos, Jesús M., Marti-Fabregas, Joan, Aguilera-Simón, Ana, Planas, Anna M., DeDiego, Marta L., Felipe Mimbrera, Alicia de, Masjuan, Jaime, García-Madrona, Sebastián, Segura, Tomás, González-Villar, Esther, Serrano-Heras, Gemma, Domínguez-Mayoral, Ana, Menéndez-Valladares, Paloma, Montaner, Joan, Migeotte, Isabelle, Rahmouni, Souad, Darcis, Gilles, Bernardo, David, Rojo, Silvia, Schulte, Eva C., Protzer, Ulrike, Fricke, Lisa, Winter, Christof, Niemi, Mari, Cordioli, Mattia, Delgado, Pilar, Fernández-Cadenas, Israel, CSIC - Plataforma Temática Interdisciplinar del CSIC Salud Global (PTI Salud Global), European Commission, Instituto de Salud Carlos III, Generalitat de Catalunya, National Fund for Scientific Research (Belgium), Fonds Léon Fredericq, Llucià-Carol, Laia, Muiño, Elena, Cullell, Nàtalia, Cárcel-Márquez, Jara, Lledós, Miquel, Gallego-Fabrega, Cristina, Martín-Campos, Jesús M., Marti-Fabregas, Joan, Aguilera-Simón, Ana, Planas, Anna M., DeDiego, Marta L., Felipe Mimbrera, Alicia de, Masjuan, Jaime, García-Madrona, Sebastián, Segura, Tomás, González-Villar, Esther, Serrano-Heras, Gemma, Domínguez-Mayoral, Ana, Menéndez-Valladares, Paloma, Montaner, Joan, Migeotte, Isabelle, Rahmouni, Souad, Darcis, Gilles, Bernardo, David, Rojo, Silvia, Schulte, Eva C., Protzer, Ulrike, Fricke, Lisa, Winter, Christof, Niemi, Mari, Cordioli, Mattia, Delgado, Pilar, and Fernández-Cadenas, Israel

Abstract

We aimed to analyse whether patients with ischaemic stroke (IS) occurring within eight days after the onset of COVID-19 (IS-COV) are associated with a specific aetiology of IS. We used SUPERGNOVA to identify genome regions that correlate between the IS-COV cohort (73 IS-COV cases vs. 701 population controls) and different aetiological subtypes. Polygenic risk scores (PRSs) for each subtype were generated and tested in the IS-COV cohort using PRSice-2 and PLINK to find genetic associations. Both analyses used the IS-COV cohort and GWAS from MEGASTROKE (67,162 stroke patients vs. 454,450 population controls), GIGASTROKE (110,182 vs. 1,503,898), and the NINDS Stroke Genetics Network (16,851 vs. 32,473). Three genomic regions were associated (p-value < 0.05) with large artery atherosclerosis (LAA) and cardioembolic stroke (CES). We found four loci targeting the genes PITX2 (rs10033464, IS-COV beta = 0.04, p-value = 2.3 × 10−2, se = 0.02), previously associated with CES, HS6ST1 (rs4662630, IS-COV beta = −0.04, p-value = 1.3 × 10−3, se = 0.01), TMEM132E (rs12941838 IS-COV beta = 0.05, p-value = 3.6 × 10−4, se = 0.01), and RFFL (rs797989 IS-COV beta = 0.03, p-value = 1.0 × 10−2, se = 0.01). A statistically significant PRS was observed for LAA. Our results suggest that IS-COV cases are genetically similar to LAA and CES subtypes. Larger cohorts are needed to assess if the genetic factors in IS-COV cases are shared with the general population or specific to viral infection.

Published
2023

23. Table_2_A Polygenic Risk Score Based on a Cardioembolic Stroke Multitrait Analysis Improves a Clinical Prediction Model for This Stroke Subtype.XLSX

Author

Cárcel-Márquez, Jara, Muiño, Elena, Gallego-Fabrega, Cristina, Cullell, Nàtalia, Lledós, Miquel, Llucià-Carol, Laia, Sobrino, Tomás, Campos, Francisco, Castillo, José, Freijo-Guerrero, Maria del Mar, Arenillas, Juan F., Obach, Víctor, Álvarez-Sabín, José, Molina, Carlos A., Ribó, Marc, Jiménez-Conde, Jordi, Roquer, Jaume, Muñoz-Narbona, Lucía, López-Cancio, Elena, Millán, Mónica, Díaz-Navarro, Rosa M., Vives-Bauzá, Cristòfol, Serrano-Heras, Gemma, Segura, Tomás, Ibáñez, Laura, Heitsch, Laura, Delgado, Pilar, Dhar, Rajat, Krupinski, Jerzy, Delgado-Mederos, Raquel, Prats-Sánchez, Luis, Camps-Renom, Pol, Blay, Natalia, Sumoy, Lauro, Cid, Rafael de, Montaner, Joan, Cruchaga, Carlos, Lee, Jin-Moo, Marti-Fabregas, Joan, Fernández-Cadenas, Israel, Cárcel-Márquez, Jara, Muiño, Elena, Gallego-Fabrega, Cristina, Cullell, Nàtalia, Lledós, Miquel, Llucià-Carol, Laia, Sobrino, Tomás, Campos, Francisco, Castillo, José, Freijo-Guerrero, Maria del Mar, Arenillas, Juan F., Obach, Víctor, Álvarez-Sabín, José, Molina, Carlos A., Ribó, Marc, Jiménez-Conde, Jordi, Roquer, Jaume, Muñoz-Narbona, Lucía, López-Cancio, Elena, Millán, Mónica, Díaz-Navarro, Rosa M., Vives-Bauzá, Cristòfol, Serrano-Heras, Gemma, Segura, Tomás, Ibáñez, Laura, Heitsch, Laura, Delgado, Pilar, Dhar, Rajat, Krupinski, Jerzy, Delgado-Mederos, Raquel, Prats-Sánchez, Luis, Camps-Renom, Pol, Blay, Natalia, Sumoy, Lauro, Cid, Rafael de, Montaner, Joan, Cruchaga, Carlos, Lee, Jin-Moo, Marti-Fabregas, Joan, and Fernández-Cadenas, Israel

Abstract

[Background] Occult atrial fibrillation (AF) is one of the major causes of embolic stroke of undetermined source (ESUS). Knowing the underlying etiology of an ESUS will reduce stroke recurrence and/or unnecessary use of anticoagulants. Understanding cardioembolic strokes (CES), whose main cause is AF, will provide tools to select patients who would benefit from anticoagulants among those with ESUS or AF. We aimed to discover novel loci associated with CES and create a polygenetic risk score (PRS) for a more efficient CES risk stratification., [Methods] Multitrait analysis of GWAS (MTAG) was performed with MEGASTROKE-CES cohort (n = 362,661) and AF cohort (n = 1,030,836). We considered significant variants and replicated those variants with MTAG p-value < 5 × 10−8 influencing both traits (GWAS-pairwise) with a p-value < 0.05 in the original GWAS and in an independent cohort (n = 9,105). The PRS was created with PRSice-2 and evaluated in the independent cohort., [Results] We found and replicated eleven loci associated with CES. Eight were novel loci. Seven of them had been previously associated with AF, namely, CAV1, ESR2, GORAB, IGF1R, NEURL1, WIPF1, and ZEB2. KIAA1755 locus had never been associated with CES/AF, leading its index variant to a missense change (R1045W). The PRS generated has been significantly associated with CES improving discrimination and patient reclassification of a model with age, sex, and hypertension., [Conclusion] The loci found significantly associated with CES in the MTAG, together with the creation of a PRS that improves the predictive clinical models of CES, might help guide future clinical trials of anticoagulant therapy in patients with ESUS or AF.

Published
2022

24. Additional file 1 of Altered methylation pattern in EXOC4 is associated with stroke outcome: an epigenome-wide association study

Author

Boehringer Ingelheim Fonds, Instituto de Salud Carlos III, Agència de Gestió d'Ajuts Universitaris i de Recerca, Bristol-Myers Squibb, Fundació La Marató de TV3, Fundació Docència i Recerca MútuaTerrassa, Cullell, Nàtalia, Soriano-Tárraga, Carolina, Gallego-Fabrega, Cristina, Cárcel-Márquez, Jara, Muiño, Elena, Llucià-Carol, Laia, Lledós, Miquel, Esteller, Manel, Moura, Manuel Castro de, Montaner, Joan, Rosell, Anna, Delgado, Pilar, Marti-Fabregas, Joan, Krupinski, Jerzy, Roquer, Jaume, Jiménez-Conde, Jordi, Fernández-Cadenas, Israel, Boehringer Ingelheim Fonds, Instituto de Salud Carlos III, Agència de Gestió d'Ajuts Universitaris i de Recerca, Bristol-Myers Squibb, Fundació La Marató de TV3, Fundació Docència i Recerca MútuaTerrassa, Cullell, Nàtalia, Soriano-Tárraga, Carolina, Gallego-Fabrega, Cristina, Cárcel-Márquez, Jara, Muiño, Elena, Llucià-Carol, Laia, Lledós, Miquel, Esteller, Manel, Moura, Manuel Castro de, Montaner, Joan, Rosell, Anna, Delgado, Pilar, Marti-Fabregas, Joan, Krupinski, Jerzy, Roquer, Jaume, Jiménez-Conde, Jordi, and Fernández-Cadenas, Israel

Published
2022

25. Supplementary Material DNA methylation is associated with ischemic stroke risk: An Epigenome-Wide association study

Author

Cullell, Nàtalia, Soriano-Tárraga, Carolina, Gallego-Fabrega, Cristina, Cárcel-Márquez, Jara, Torres-Águila, Nuria P., Muiño, Elena, Lledós, Miquel, Llucià-Carol, Laia, Esteller, Manel, Castro de Moura, Manuel, Montaner, Joan, Fernández-Sanlés, Alba, Elosua, Roberto, Delgado, Pilar, Marti-Fabregas, Joan, Krupinski, Jerzy, Roquer, Jaume, Jiménez-Conde, Jordi, Fernández-Cadenas, Israel, Cullell, Nàtalia, Soriano-Tárraga, Carolina, Gallego-Fabrega, Cristina, Cárcel-Márquez, Jara, Torres-Águila, Nuria P., Muiño, Elena, Lledós, Miquel, Llucià-Carol, Laia, Esteller, Manel, Castro de Moura, Manuel, Montaner, Joan, Fernández-Sanlés, Alba, Elosua, Roberto, Delgado, Pilar, Marti-Fabregas, Joan, Krupinski, Jerzy, Roquer, Jaume, Jiménez-Conde, Jordi, and Fernández-Cadenas, Israel

Abstract

1-Supplementary Methods 1.1-Cohorts included in the study 2-e-Table legends 3-e-Figure legends 4-e-Tables 5-e-Figures 6-e-References

Published
2022

26. Supplemental Material Biological age acceleration is lower in women with Ischemic Stroke compared to men

Author

Gallego-Fabrega, Cristina, Muiño, Elena, Cullell, Nàtalia, Cárcel-Márquez, Jara, Lazcano, Eduardo, Soriano-Tárraga, Carolina, Lledós, Miquel, Llucià-Carol, Laia, Aguilera-Simón, Ana, Marín, Rebeca, Prats-Sánchez, Luis, Camps-Renom, Pol, Delgado-Mederos, Raquel, Martín-Campos, Jesús M., Delgado Hito, Pilar, Marti-Fabregas, Joan, Montaner, Joan, Krupinski, Jerzy, Jiménez-Conde, J., Roquer, Jaume, Fernández-Cadenas, Israel, Gallego-Fabrega, Cristina, Muiño, Elena, Cullell, Nàtalia, Cárcel-Márquez, Jara, Lazcano, Eduardo, Soriano-Tárraga, Carolina, Lledós, Miquel, Llucià-Carol, Laia, Aguilera-Simón, Ana, Marín, Rebeca, Prats-Sánchez, Luis, Camps-Renom, Pol, Delgado-Mederos, Raquel, Martín-Campos, Jesús M., Delgado Hito, Pilar, Marti-Fabregas, Joan, Montaner, Joan, Krupinski, Jerzy, Jiménez-Conde, J., Roquer, Jaume, and Fernández-Cadenas, Israel

Published
2022

27. A Polygenic Risk Score Based on a Cardioembolic Stroke Multitrait Analysis Improves a Clinical Prediction Model for This Stroke Subtype

Author

National Institutes of Health (US), National Cancer Institute (US), National Human Genome Research Institute (US), National Heart, Lung, and Blood Institute (US), National Institute on Drug Abuse (US), National Institute of Mental Health (US), National Institute of Neurological Disorders and Stroke (US), Cárcel-Márquez, Jara, Muiño, Elena, Gallego-Fabrega, Cristina, Cullell, Nàtalia, Lledós, Miquel, Llucià-Carol, Laia, Sobrino, Tomás, Campos, Francisco, Castillo, José, Freijo-Guerrero, Maria del Mar, Arenillas, Juan F., Obach, Víctor, Álvarez-Sabín, José, Molina, Carlos A., Ribó, Marc, Jiménez-Conde, Jordi, Roquer, Jaume, Muñoz-Narbona, Lucía, López-Cancio, Elena, Millán, Mónica, Díaz-Navarro, Rosa M., Vives-Bauzá, Cristòfol, Serrano-Heras, Gemma, Segura, Tomás, Ibáñez, Laura, Heitsch, Laura, Delgado, Pilar, Dhar, Rajat, Krupinski, Jerzy, Delgado-Mederos, Raquel, Prats-Sánchez, Luis, Camps-Renom, Pol, Blay, Natalia, Sumoy, Lauro, Cid, Rafael de, Montaner, Joan, Cruchaga, Carlos, Lee, Jin-Moo, Marti-Fabregas, Joan, Fernández-Cadenas, Israel, National Institutes of Health (US), National Cancer Institute (US), National Human Genome Research Institute (US), National Heart, Lung, and Blood Institute (US), National Institute on Drug Abuse (US), National Institute of Mental Health (US), National Institute of Neurological Disorders and Stroke (US), Cárcel-Márquez, Jara, Muiño, Elena, Gallego-Fabrega, Cristina, Cullell, Nàtalia, Lledós, Miquel, Llucià-Carol, Laia, Sobrino, Tomás, Campos, Francisco, Castillo, José, Freijo-Guerrero, Maria del Mar, Arenillas, Juan F., Obach, Víctor, Álvarez-Sabín, José, Molina, Carlos A., Ribó, Marc, Jiménez-Conde, Jordi, Roquer, Jaume, Muñoz-Narbona, Lucía, López-Cancio, Elena, Millán, Mónica, Díaz-Navarro, Rosa M., Vives-Bauzá, Cristòfol, Serrano-Heras, Gemma, Segura, Tomás, Ibáñez, Laura, Heitsch, Laura, Delgado, Pilar, Dhar, Rajat, Krupinski, Jerzy, Delgado-Mederos, Raquel, Prats-Sánchez, Luis, Camps-Renom, Pol, Blay, Natalia, Sumoy, Lauro, Cid, Rafael de, Montaner, Joan, Cruchaga, Carlos, Lee, Jin-Moo, Marti-Fabregas, Joan, and Fernández-Cadenas, Israel

Abstract

Occult atrial fibrillation (AF) is one of the major causes of embolic stroke of undetermined source (ESUS). Knowing the underlying etiology of an ESUS will reduce stroke recurrence and/or unnecessary use of anticoagulants. Understanding cardioembolic strokes (CES), whose main cause is AF, will provide tools to select patients who would benefit from anticoagulants among those with ESUS or AF. We aimed to discover novel loci associated with CES and create a polygenetic risk score (PRS) for a more efficient CES risk stratification.

Published
2022

28. Biological Age Acceleration Is Lower in Women with Ischemic Stroke Compared to Men

Author

Instituto de Salud Carlos III, Fundació La Marató de TV3, Generalitat de Catalunya, European Commission, Gallego-Fabrega, Cristina, Muiño, Elena, Cullell, Nàtalia, Cárcel-Márquez, Jara, Lazcano, Eduardo, Soriano-Tárraga, Carolina, Lledós, Miquel, Llucià-Carol, Laia, Aguilera-Simón, Ana, Marín, Rebeca, Prats-Sánchez, Luis, Camps-Renom, Pol, Delgado-Mederos, Raquel, Martín-Campos, Jesús M., Delgado Hito, Pilar, Marti-Fabregas, Joan, Montaner, Joan, Krupinski, Jerzy, Jiménez-Conde, J., Roquer, Jaume, Fernández-Cadenas, Israel, Instituto de Salud Carlos III, Fundació La Marató de TV3, Generalitat de Catalunya, European Commission, Gallego-Fabrega, Cristina, Muiño, Elena, Cullell, Nàtalia, Cárcel-Márquez, Jara, Lazcano, Eduardo, Soriano-Tárraga, Carolina, Lledós, Miquel, Llucià-Carol, Laia, Aguilera-Simón, Ana, Marín, Rebeca, Prats-Sánchez, Luis, Camps-Renom, Pol, Delgado-Mederos, Raquel, Martín-Campos, Jesús M., Delgado Hito, Pilar, Marti-Fabregas, Joan, Montaner, Joan, Krupinski, Jerzy, Jiménez-Conde, J., Roquer, Jaume, and Fernández-Cadenas, Israel

Abstract

Background: Stroke onset in women occurs later in life compared with men. The underlying mechanisms of these differences have not been established. Epigenetic clocks, based on DNA methylation (DNAm) profiles, are the most accurate biological age estimate. Epigenetic age acceleration (EAA) measures indicate whether an individual is biologically younger or older than expected. Our aim was to analyze whether sexual dichotomy at age of stroke onset is conditioned by EAA. Methods: We used 2 DNAm datasets from whole blood samples of case-control genetic studies of ischemic stroke (IS), a discovery cohort of 374 IS patients (N women=163, N men=211), from GRECOS (Genotyping Recurrence Risk of Stroke) and SEDMAN (Dabigatran Study in the Early Phase of Stroke, New Neuroimaging Markers and Biomarkers) studies and a replication cohort of 981 IS patients (N women=411, N men=570) from BASICMAR register. We compared chronological age, 2 DNAm-based biomarkers of aging and intrinsic and extrinsic epigenetic age acceleration EAA (IEAA and extrinsic EAA, respectively), in IS as well as in individual IS etiologic subtypes. Horvath and Hannum epigenetic clocks were used to assess the aging rate. A proteomic study using the SOMAScan multiplex assay was performed on 26 samples analyzing 1305 proteins. Results: Women present lower Hannum-extrinsic EAA values, whereas men have higher Hannum-extrinsic EAA values (women=-0.64, men=1.24, P=1.34×10); the same tendency was observed in the second cohort (women=-0.57, men=0.79, P=0.02). These differences seemed to be specific to cardioembolic and undetermined stroke subtypes. Additionally, 42 blood protein levels were associated with Hannum-extrinsic EAA (P<0.05), belonging to the immune effector process (P=1.54×10) and platelet degranulation (P<8.74×10) pathways. Conclusions: This study shows that sex-specific underlying biological mechanisms associated with stroke onset could be due to differences in biological age acceleration between men and w

Published
2022

29. DNA Methylation and Ischemic Stroke Risk: An Epigenome-Wide Association Study

Author

Instituto de Salud Carlos III, Fundació La Marató de TV3, Fundació Docència i Recerca MútuaTerrassa, European Commission, Generalitat de Catalunya, Cullell, Nàtalia, Soriano-Tárraga, Carolina, Gallego-Fabrega, Cristina, Cárcel-Márquez, Jara, Torres-Águila, Nuria P., Muiño, Elena, Lledós, Miquel, Llucià-Carol, Laia, Esteller, Manel, Castro de Moura, Manuel, Montaner, Joan, Fernández-Sanlés, Alba, Elosua, Roberto, Delgado, Pilar, Marti-Fabregas, Joan, Krupinski, Jerzy, Roquer, Jaume, Jiménez-Conde, Jordi, Fernández-Cadenas, Israel, Instituto de Salud Carlos III, Fundació La Marató de TV3, Fundació Docència i Recerca MútuaTerrassa, European Commission, Generalitat de Catalunya, Cullell, Nàtalia, Soriano-Tárraga, Carolina, Gallego-Fabrega, Cristina, Cárcel-Márquez, Jara, Torres-Águila, Nuria P., Muiño, Elena, Lledós, Miquel, Llucià-Carol, Laia, Esteller, Manel, Castro de Moura, Manuel, Montaner, Joan, Fernández-Sanlés, Alba, Elosua, Roberto, Delgado, Pilar, Marti-Fabregas, Joan, Krupinski, Jerzy, Roquer, Jaume, Jiménez-Conde, Jordi, and Fernández-Cadenas, Israel

Abstract

Background Ischemic stroke (IS) risk heritability is partly explained by genetics. Other heritable factors, such as epigenetics, could explain an unknown proportion of the IS risk. The objective of this study is to evaluate DNA methylation association with IS using epigenome-wide association studies (EWAS). Methods We performed a two-stage EWAS comprising 1,156 subjects. Differentially methylated positions (DMPs) and differentially methylated regions (DMRs) were assessed using the Infinium 450K and EPIC BeadChip in the discovery cohort (252 IS and 43 controls). Significant DMPs were replicated in an independent cohort (618 IS and 243 controls). Stroke subtype associations were also evaluated. Differentially methylated cell-type (DMCT) was analyzed in the replicated CpG sites using EpiDISH. We additionally performed pathway enrichment analysis and causality analysis with Mendelian randomization for the replicated CpG sites. Results A total of 957 CpG sites were epigenome-wide-significant (p ≤ 10 ) in the discovery cohort, being CpG sites in the top signals (logFC = 0.058, p = 2.35 × 10 ; logFC = 0.035, p = 3.22 × 10 , respectively). ZFHX3 and MAP3K1 were among the most significant DMRs. In addition, 697 CpG sites were replicated considering Bonferroni-corrected p -values (p < 5.22 × 10 ). All the replicated DMPs were associated with risk of cardioembolic, atherothrombotic, and undetermined stroke. The DMCT analysis demonstrated that the significant associations were driven by natural killer cells. The pathway enrichment analysis showed overrepresentation of genes belonging to certain pathways including oxidative stress. ZFHX3 and MAP3K1 methylation was causally associated with specific stroke-subtype risk. Conclusion Specific DNA methylation pattern is causally associated with IS risk. These results could be useful for specifically predicting stroke occurrence and could potentially be evaluated as therapeutic targets.

Published
2022

30. Stroke genetics informs drug discovery and risk prediction across ancestries

Author

Mishra, Aniket, Malik, Rainer, Hachiya, Tsuyoshi, Jurgenson, Tuuli, Namba, Shinichi, Posner, Daniel C, Kamanu, Frederick K, Koido, Masaru, Le Grand, Quentin, Shi, Mingyang, He, Yunye, Georgakis, Marios K, Caro, Ilana, Krebs, Kristi, Liaw, Yi-Ching, Vaura, Felix C, Lin, Kuang, Winsvold, Bendik Slagsvold, Srinivasasainagendra, Vinodh, Parodi, Livia, Bae, Hee-Joon, Chauhan, Ganesh, Chong, Michael R, Tomppo, Liisa, Akinyemi, Rufus, Roshchupkin, Gennady V, Habib, Naomi, Jee, Yon Ho, Thomassen, Jesper Qvist, Abedi, Vida, Carcel-Marquez, Jara, Nygaard, Marianne, Leonard, Hampton L, Yang, Chaojie, Yonova-Doing, Ekaterina, Knol, Maria J, Lewis, Adam J, Judy, Renae L, Ago, Tetsuro, Amouyel, Philippe, Armstrong, Nicole D, Bakker, Mark K, Bartz, Traci M, Bennett, David A, Bis, Joshua C, Bordes, Constance, Borte, Sigrid, Cain, Anael, Ridker, Paul M, Cho, Kelly, Chen, Zhengming, Cruchaga, Carlos, Cole, John W, de Jager, Phil L, de Cid, Rafael, Endres, Matthias, Ferreira, Leslie E, Geerlings, Mirjam I, Gasca, Natalie C, Gudnason, Vilmundur, Hata, Jun, He, Jing, Heath, Alicia K, Ho, Yuk-Lam, Havulinna, Aki S, Hopewell, Jemma C, Hyacinth, Hyacinth I, Inouye, Michael, Jacob, Mina A, Jeon, Christina E, Jern, Christina, Kamouchi, Masahiro, Keene, Keith L, Kitazono, Takanari, Kittner, Steven J, Konuma, Takahiro, Kumar, Amit, Lacaze, Paul, Launer, Lenore J, Lee, Keon-Joo, Lepik, Kaido, Li, Jiang, Li, Liming, Manichaikul, Ani, Markus, Hugh S, Marston, Nicholas A, Meitinger, Thomas, Mitchell, Braxton D, Montellano, Felipe A, Morisaki, Takayuki, Mosley, Thomas H, Nalls, Mike A, Nordestgaard, Borge G, O'Donnell, Martin J, Okada, Yukinori, Onland-Moret, N Charlotte, Ovbiagele, Bruce, Peters, Annette, Psaty, Bruce M, Rich, Stephen S, Rosand, Jonathan, Sabatine, Marc S, Sacco, Ralph L, Saleheen, Danish, Sandset, Else Charlotte, Salomaa, Veikko, Sargurupremraj, Muralidharan, Sasaki, Makoto, Satizabal, Claudia L, Schmidt, Carsten O, Shimizu, Atsushi, Smith, Nicholas L, Sloane, Kelly L, Sutoh, Yoichi, Sun, Yan V, Tanno, Kozo, Tiedt, Steffen, Tatlisumak, Turgut, Torres-Aguila, Nuria P, Tiwari, Hemant K, Tregouet, David-Alexandre, Trompet, Stella, Tuladhar, Anil Man, Tybjaerg-Hansen, Anne, van Vugt, Marion, Vibo, Riina, Verma, Shefali S, Wiggins, Kerri L, Wennberg, Patrik, Woo, Daniel, Wilson, Peter WF, Xu, Huichun, Yang, Qiong, Yoon, Kyungheon, Lee, Jin-Moo, Cheng, Yu-Ching, Meschia, James F, Chen, Wei Min, Sale, Michele M, Zonderman, Alan B, Evans, Michele K, Wilson, James G, Correa, Adolfo, Traylor, Matthew, Lewis, Cathryn M, Carty, Cara L, Reiner, Alexander, Haessler, Jeffrey, Langefeld, Carl D, Gottesman, Rebecca F, Yaffe, Kristine, Liu, Yong Mei, Kooperberg, Charles, Lange, Leslie A, Furie, Karen L, Arnett, Donna K, Benavente, Oscar R, Grewal, Raji P, Peddareddygari, Leema Reddy, Hveem, Kristian, Lindstrom, Sara, Wang, Lu, Smith, Erin N, Gordon, William, van Hylckama Vlieg, Astrid, de Andrade, Mariza, Brody, Jennifer A, Pattee, Jack W, Brumpton, Ben M, Suchon, Pierre, Chen, Ming-Huei, Frazer, Kelly A, Turman, Constance, Germain, Marine, MacDonald, James, Braekkan, Sigrid K, Armasu, Sebastian M, Pankratz, Nathan, Jackson, Rebecca D, Nielsen, Jonas B, Giulianini, Franco, Puurunen, Marja K, Ibrahim, Manal, Heckbert, Susan R, Bammler, Theo K, McCauley, Bryan M, Taylor, Kent D, Pankow, James S, Reiner, Alexander P, Gabrielsen, Maiken E, Deleuze, Jean-Francois, O'Donnell, Chris J, Kim, Jihye, McKnight, Barbara, Kraft, Peter, Hansen, John-Bjarne, Rosendaal, Frits R, Heit, John A, Tang, Weihong, Morange, Pierre-Emmanuel, Johnson, Andrew D, Kabrhel, Christopher, van Dijk, Ewoud J, Koudstaal, Peter J, Luijckx, Gert-Jan, Nederkoorn, Paul J, van Oostenbrugge, Robert J, Visser, Marieke C, Wermer, Marieke JH, Kappelle, L Jaap, Esko, Tonu, Metspalu, Andres, Magi, Reedik, Nelis, Mari, Irvin, Marguerite R, de Leeuw, Frank-Erik, Levi, Christopher R, Maguire, Jane, Jimenez-Conde, Jordi, Sharma, Pankaj, Sudlow, Cathie LM, Rannikmae, Kristiina, Schmidt, Reinhold, Slowik, Agnieszka, Pera, Joanna, Thijs, Vincent NS, Lindgren, Arne G, Ilinca, Andreea, Melander, Olle, Engstrom, Gunnar, Rexrode, Kathryn M, Rothwell, Peter M, Stanne, Tara M, Johnson, Julie A, Danesh, John, Butterworth, Adam S, Heitsch, Laura, Boncoraglio, Giorgio B, Kubo, Michiaki, Pezzini, Alessandro, Rolfs, Arndt, Giese, Anne-Katrin, Weir, David, Ross, Owen A, Lemmons, Robin, Soderholm, Martin, Cushman, Mary, Jood, Katarina, McDonough, Caitrin W, Bell, Steven, Linkohr, Birgit, Lee, Tsong-Hai, Putaala, Jukka, Anderson, Christopher D, Lopez, Oscar L, Jian, Xueqiu, Schminke, Ulf, Cullell, Natalia, Delgado, Pilar, Ibanez, Laura, Krupinski, Jerzy, Lioutas, Vasileios, Matsuda, Koichi, Montaner, Joan, Muino, Elena, Roquer, Jaume, Sarnowski, Chloe, Sattar, Naveed, Sibolt, Gerli, Teumer, Alexander, Rutten-Jacobs, Loes, Kanai, Masahiro, Gretarsdottir, Solveig, Rost, Natalia S, Yusuf, Salim, Almgren, Peter, Ay, Hakan, Bevan, Steve, Brown, Robert D, Carrera, Caty, Buring, Julie E, Chen, Wei-Min, Cotlarciuc, Ioana, de Bakker, Paul IW, DeStefano, Anita L, den Hoed, Marcel, Duan, Qing, Engelter, Stefan T, Falcone, Guido J, Gustafsson, Stefan, Hassan, Ahamad, Holliday, Elizabeth G, Howard, George, Hsu, Fang-Chi, Ingelsson, Erik, Harris, Tamara B, Kissela, Brett M, Kleindorfer, Dawn O, Langenberg, Claudia, Lemmens, Robin, Leys, Didier, Lin, Wei-Yu, Lorentzen, Erik, Magnusson, Patrik K, McArdle, Patrick F, Pulit, Sara L, Rice, Kenneth, Sakaue, Saori, Sapkota, Bishwa R, Tanislav, Christian, Thorleifsson, Gudmar, Thorsteinsdottir, Unnur, Tzourio, Christophe, van Duijn, Cornelia M, Walters, Matthew, Wareham, Nicholas J, Amin, Najaf, Aparicio, Hugo J, Attia, John, Beiser, Alexa S, Berr, Claudine, Bustamante, Mariana, Caso, Valeria, Choi, Seung Hoan, Chowhan, Ayesha, Dartigues, Jean-Francois, Delavaran, Hossein, Dorr, Marcus, Ford, Ian, Gurpreet, Wander S, Hamsten, Anders, Hozawa, Atsushi, Ingelsson, Martin, Iwasaki, Motoki, Kaffashian, Sara, Kalra, Lalit, Kjartansson, Olafur, Kloss, Manja, Labovitz, Daniel L, Laurie, Cathy C, Li, Linxin, Lind, Lars, Lindgren, Cecilia M, Makoto, Hirata, Minegishi, Naoko, Morris, Andrew P, Muller-Nurasyid, Martina, Norrving, Bo, Ogishima, Soichi, Parati, Eugenio A, Pedersen, Nancy L, Perola, Markus, Jousilahti, Pekka, Pileggi, Silvana, Rabionet, Raquel, Riba-Llena, Iolanda, Ribases, Marta, Romero, Jose R, Rudd, Anthony G, Sarin, Antti-Pekka, Sarju, Ralhan, Satoh, Mamoru, Sawada, Norie, Sigurdsson, Asgeir, Smith, Albert, Stine, O Colin, Stott, David J, Strauch, Konstantin, Takai, Takako, Tanaka, Hideo, Touze, Emmanuel, Tsugane, Shoichiro, Uitterlinden, Andre G, Valdimarsson, Einar M, van der Lee, Sven J, Wakai, Kenji, Williams, Stephen R, Wolfe, Charles DA, Wong, Quenna, Yamaji, Taiki, Sanghera, Dharambir K, Stefansson, Kari, Martinez-Majander, Nicolas, Sobue, Kenji, Soriano-Tarraga, Carolina, Volzke, Henry, Akpa, Onoja, Sarfo, Fred S, Akpalu, Albert, Obiako, Reginald, Wahab, Kolawole, Osaigbovo, Godwin, Owolabi, Lukman, Komolafe, Morenikeji, Jenkins, Carolyn, Arulogun, Oyedunni, Ogbole, Godwin, Adeoye, Abiodun M, Akinyemi, Joshua, Agunloye, Atinuke, Fakunle, Adekunle G, Uvere, Ezinne, Olalere, Abimbola, Adebajo, Olayinka J, Chen, Junshi, Clarke, Robert, Collins, Rory, Guo, Yu, Wang, Chen, Lv, Jun, Peto, Richard, Chen, Yiping, Fairhurst-Hunter, Zammy, Hill, Michael, Pozarickij, Alfred, Schmidt, Dan, Stevens, Becky, Turnbull, Iain, Yu, Canqing, Nagai, Akiko, Murakami, Yoishinori, Shiroma, Eric J, Sigurdsson, Sigurdur, Ghanbari, Mohsen, Boerwinkle, Eric, Fongang, Bernard, Wang, Ruiqi, Ikram, Mohammad K, Volker, Uwe, de Laat, Karlijn F, van Norden, Anouk GW, de Kort, Paul L, Vermeer, Sarah E, Brouwers, Paul JAM, Gons, Rob AR, den Heijer, Tom, van Dijk, Gert W, van Rooij, Frank GW, Aamodt, Anne H, Skogholt, Anne H, Willer, Cristen J, Heuch, Ingrid, Hagen, Knut, Fritsche, Lars G, Pedersen, Linda M, Ellekjaer, Hanne, Zhou, Wei, Martinsen, Amy E, Kristoffersen, Espen S, Thomas, Laurent F, Kleinschnitz, Christoph, Frantz, Stefan, Ungethum, Kathrin, Gallego-Fabrega, Cristina, Lledos, Miquel, Llucia-Carol, Laia, Sobrino, Tomas, Campos, Francisco, Castillo, Jose, Freijo, Marimar, Arenillas, Juan Francisco, Obach, Victor, Alvarez-Sabin, Jose, Molina, Carlos A, Ribo, Marc, Munoz-Narbona, Lucia, Lopez-Cancio, Elena, Millan, Monica, Diaz-Navarro, Rosa, Vives-Bauza, Cristofol, Serrano-Heras, Gemma, Segura, Tomas, Dhar, Rajat, Delgado-Mederos, Raquel, Prats-Sanchez, Luis, Camps-Renom, Pol, Blay, Natalia, Sumoy, Lauro, Marti-Fabregas, Joan, Schnohr, Peter, Jensen, Gorm B, Benn, Marianne, Afzal, Shoaib, Kamstrup, Pia R, van Setten, Jessica, van der Laan, Sander W, Vonk, Jet MJ, Kim, Bong-Jo, Curtze, Sami, Tiainen, Marjaana, Kinnunen, Janne, Menon, Vilas, Sung, Yun Ju, Yang, Chengran, Saillour-Glenisson, Florence, Gravel, Simon, Millwood, Iona Y, Gieger, Christian, Ninomiya, Toshiharu, Grabe, Hans J, Jukema, J Wouter, Rissanen, Ina L, Strbian, Daniel, Kim, Young Jin, Chen, Pei-Hsin, Mayerhofer, Ernst, Howson, Joanna MM, Adams, Hieab, Wassertheil-Smoller, Sylvia, Christensen, Kaare, Ikram, Mohammad A, Rundek, Tatjana, Worrall, Bradford B, Lathrop, G Mark, Riaz, Moeen, Simonsick, Eleanor M, Korv, Janika, Franca, Paulo HC, Zand, Ramin, Prasad, Kameshwar, Frikke-Schmidt, Ruth, Liman, Thomas, Haeusler, Karl Georg, Ruigrok, Ynte M, Heuschmann, Peter Ulrich, Longstreth, WT, Jung, Keum Ji, Bastarache, Lisa, Pare, Guillaume, Damrauer, Scott M, Chasman, Daniel I, Rotter, Jerome I, Zwart, John-Anker, Niiranen, Teemu J, Fornage, Myriam, Liaw, Yung-Po, Seshadri, Sudha, Fernandez-Cadenas, Israel, Walters, Robin G, Ruff, Christian T, Owolabi, Mayowa O, Huffman, Jennifer E, Milani, Lili, Kamatani, Yoichiro, Dichgans, Martin, Debette, Stephanie, Mishra, Aniket, Malik, Rainer, Hachiya, Tsuyoshi, Jurgenson, Tuuli, Namba, Shinichi, Posner, Daniel C, Kamanu, Frederick K, Koido, Masaru, Le Grand, Quentin, Shi, Mingyang, He, Yunye, Georgakis, Marios K, Caro, Ilana, Krebs, Kristi, Liaw, Yi-Ching, Vaura, Felix C, Lin, Kuang, Winsvold, Bendik Slagsvold, Srinivasasainagendra, Vinodh, Parodi, Livia, Bae, Hee-Joon, Chauhan, Ganesh, Chong, Michael R, Tomppo, Liisa, Akinyemi, Rufus, Roshchupkin, Gennady V, Habib, Naomi, Jee, Yon Ho, Thomassen, Jesper Qvist, Abedi, Vida, Carcel-Marquez, Jara, Nygaard, Marianne, Leonard, Hampton L, Yang, Chaojie, Yonova-Doing, Ekaterina, Knol, Maria J, Lewis, Adam J, Judy, Renae L, Ago, Tetsuro, Amouyel, Philippe, Armstrong, Nicole D, Bakker, Mark K, Bartz, Traci M, Bennett, David A, Bis, Joshua C, Bordes, Constance, Borte, Sigrid, Cain, Anael, Ridker, Paul M, Cho, Kelly, Chen, Zhengming, Cruchaga, Carlos, Cole, John W, de Jager, Phil L, de Cid, Rafael, Endres, Matthias, Ferreira, Leslie E, Geerlings, Mirjam I, Gasca, Natalie C, Gudnason, Vilmundur, Hata, Jun, He, Jing, Heath, Alicia K, Ho, Yuk-Lam, Havulinna, Aki S, Hopewell, Jemma C, Hyacinth, Hyacinth I, Inouye, Michael, Jacob, Mina A, Jeon, Christina E, Jern, Christina, Kamouchi, Masahiro, Keene, Keith L, Kitazono, Takanari, Kittner, Steven J, Konuma, Takahiro, Kumar, Amit, Lacaze, Paul, Launer, Lenore J, Lee, Keon-Joo, Lepik, Kaido, Li, Jiang, Li, Liming, Manichaikul, Ani, Markus, Hugh S, Marston, Nicholas A, Meitinger, Thomas, Mitchell, Braxton D, Montellano, Felipe A, Morisaki, Takayuki, Mosley, Thomas H, Nalls, Mike A, Nordestgaard, Borge G, O'Donnell, Martin J, Okada, Yukinori, Onland-Moret, N Charlotte, Ovbiagele, Bruce, Peters, Annette, Psaty, Bruce M, Rich, Stephen S, Rosand, Jonathan, Sabatine, Marc S, Sacco, Ralph L, Saleheen, Danish, Sandset, Else Charlotte, Salomaa, Veikko, Sargurupremraj, Muralidharan, Sasaki, Makoto, Satizabal, Claudia L, Schmidt, Carsten O, Shimizu, Atsushi, Smith, Nicholas L, Sloane, Kelly L, Sutoh, Yoichi, Sun, Yan V, Tanno, Kozo, Tiedt, Steffen, Tatlisumak, Turgut, Torres-Aguila, Nuria P, Tiwari, Hemant K, Tregouet, David-Alexandre, Trompet, Stella, Tuladhar, Anil Man, Tybjaerg-Hansen, Anne, van Vugt, Marion, Vibo, Riina, Verma, Shefali S, Wiggins, Kerri L, Wennberg, Patrik, Woo, Daniel, Wilson, Peter WF, Xu, Huichun, Yang, Qiong, Yoon, Kyungheon, Lee, Jin-Moo, Cheng, Yu-Ching, Meschia, James F, Chen, Wei Min, Sale, Michele M, Zonderman, Alan B, Evans, Michele K, Wilson, James G, Correa, Adolfo, Traylor, Matthew, Lewis, Cathryn M, Carty, Cara L, Reiner, Alexander, Haessler, Jeffrey, Langefeld, Carl D, Gottesman, Rebecca F, Yaffe, Kristine, Liu, Yong Mei, Kooperberg, Charles, Lange, Leslie A, Furie, Karen L, Arnett, Donna K, Benavente, Oscar R, Grewal, Raji P, Peddareddygari, Leema Reddy, Hveem, Kristian, Lindstrom, Sara, Wang, Lu, Smith, Erin N, Gordon, William, van Hylckama Vlieg, Astrid, de Andrade, Mariza, Brody, Jennifer A, Pattee, Jack W, Brumpton, Ben M, Suchon, Pierre, Chen, Ming-Huei, Frazer, Kelly A, Turman, Constance, Germain, Marine, MacDonald, James, Braekkan, Sigrid K, Armasu, Sebastian M, Pankratz, Nathan, Jackson, Rebecca D, Nielsen, Jonas B, Giulianini, Franco, Puurunen, Marja K, Ibrahim, Manal, Heckbert, Susan R, Bammler, Theo K, McCauley, Bryan M, Taylor, Kent D, Pankow, James S, Reiner, Alexander P, Gabrielsen, Maiken E, Deleuze, Jean-Francois, O'Donnell, Chris J, Kim, Jihye, McKnight, Barbara, Kraft, Peter, Hansen, John-Bjarne, Rosendaal, Frits R, Heit, John A, Tang, Weihong, Morange, Pierre-Emmanuel, Johnson, Andrew D, Kabrhel, Christopher, van Dijk, Ewoud J, Koudstaal, Peter J, Luijckx, Gert-Jan, Nederkoorn, Paul J, van Oostenbrugge, Robert J, Visser, Marieke C, Wermer, Marieke JH, Kappelle, L Jaap, Esko, Tonu, Metspalu, Andres, Magi, Reedik, Nelis, Mari, Irvin, Marguerite R, de Leeuw, Frank-Erik, Levi, Christopher R, Maguire, Jane, Jimenez-Conde, Jordi, Sharma, Pankaj, Sudlow, Cathie LM, Rannikmae, Kristiina, Schmidt, Reinhold, Slowik, Agnieszka, Pera, Joanna, Thijs, Vincent NS, Lindgren, Arne G, Ilinca, Andreea, Melander, Olle, Engstrom, Gunnar, Rexrode, Kathryn M, Rothwell, Peter M, Stanne, Tara M, Johnson, Julie A, Danesh, John, Butterworth, Adam S, Heitsch, Laura, Boncoraglio, Giorgio B, Kubo, Michiaki, Pezzini, Alessandro, Rolfs, Arndt, Giese, Anne-Katrin, Weir, David, Ross, Owen A, Lemmons, Robin, Soderholm, Martin, Cushman, Mary, Jood, Katarina, McDonough, Caitrin W, Bell, Steven, Linkohr, Birgit, Lee, Tsong-Hai, Putaala, Jukka, Anderson, Christopher D, Lopez, Oscar L, Jian, Xueqiu, Schminke, Ulf, Cullell, Natalia, Delgado, Pilar, Ibanez, Laura, Krupinski, Jerzy, Lioutas, Vasileios, Matsuda, Koichi, Montaner, Joan, Muino, Elena, Roquer, Jaume, Sarnowski, Chloe, Sattar, Naveed, Sibolt, Gerli, Teumer, Alexander, Rutten-Jacobs, Loes, Kanai, Masahiro, Gretarsdottir, Solveig, Rost, Natalia S, Yusuf, Salim, Almgren, Peter, Ay, Hakan, Bevan, Steve, Brown, Robert D, Carrera, Caty, Buring, Julie E, Chen, Wei-Min, Cotlarciuc, Ioana, de Bakker, Paul IW, DeStefano, Anita L, den Hoed, Marcel, Duan, Qing, Engelter, Stefan T, Falcone, Guido J, Gustafsson, Stefan, Hassan, Ahamad, Holliday, Elizabeth G, Howard, George, Hsu, Fang-Chi, Ingelsson, Erik, Harris, Tamara B, Kissela, Brett M, Kleindorfer, Dawn O, Langenberg, Claudia, Lemmens, Robin, Leys, Didier, Lin, Wei-Yu, Lorentzen, Erik, Magnusson, Patrik K, McArdle, Patrick F, Pulit, Sara L, Rice, Kenneth, Sakaue, Saori, Sapkota, Bishwa R, Tanislav, Christian, Thorleifsson, Gudmar, Thorsteinsdottir, Unnur, Tzourio, Christophe, van Duijn, Cornelia M, Walters, Matthew, Wareham, Nicholas J, Amin, Najaf, Aparicio, Hugo J, Attia, John, Beiser, Alexa S, Berr, Claudine, Bustamante, Mariana, Caso, Valeria, Choi, Seung Hoan, Chowhan, Ayesha, Dartigues, Jean-Francois, Delavaran, Hossein, Dorr, Marcus, Ford, Ian, Gurpreet, Wander S, Hamsten, Anders, Hozawa, Atsushi, Ingelsson, Martin, Iwasaki, Motoki, Kaffashian, Sara, Kalra, Lalit, Kjartansson, Olafur, Kloss, Manja, Labovitz, Daniel L, Laurie, Cathy C, Li, Linxin, Lind, Lars, Lindgren, Cecilia M, Makoto, Hirata, Minegishi, Naoko, Morris, Andrew P, Muller-Nurasyid, Martina, Norrving, Bo, Ogishima, Soichi, Parati, Eugenio A, Pedersen, Nancy L, Perola, Markus, Jousilahti, Pekka, Pileggi, Silvana, Rabionet, Raquel, Riba-Llena, Iolanda, Ribases, Marta, Romero, Jose R, Rudd, Anthony G, Sarin, Antti-Pekka, Sarju, Ralhan, Satoh, Mamoru, Sawada, Norie, Sigurdsson, Asgeir, Smith, Albert, Stine, O Colin, Stott, David J, Strauch, Konstantin, Takai, Takako, Tanaka, Hideo, Touze, Emmanuel, Tsugane, Shoichiro, Uitterlinden, Andre G, Valdimarsson, Einar M, van der Lee, Sven J, Wakai, Kenji, Williams, Stephen R, Wolfe, Charles DA, Wong, Quenna, Yamaji, Taiki, Sanghera, Dharambir K, Stefansson, Kari, Martinez-Majander, Nicolas, Sobue, Kenji, Soriano-Tarraga, Carolina, Volzke, Henry, Akpa, Onoja, Sarfo, Fred S, Akpalu, Albert, Obiako, Reginald, Wahab, Kolawole, Osaigbovo, Godwin, Owolabi, Lukman, Komolafe, Morenikeji, Jenkins, Carolyn, Arulogun, Oyedunni, Ogbole, Godwin, Adeoye, Abiodun M, Akinyemi, Joshua, Agunloye, Atinuke, Fakunle, Adekunle G, Uvere, Ezinne, Olalere, Abimbola, Adebajo, Olayinka J, Chen, Junshi, Clarke, Robert, Collins, Rory, Guo, Yu, Wang, Chen, Lv, Jun, Peto, Richard, Chen, Yiping, Fairhurst-Hunter, Zammy, Hill, Michael, Pozarickij, Alfred, Schmidt, Dan, Stevens, Becky, Turnbull, Iain, Yu, Canqing, Nagai, Akiko, Murakami, Yoishinori, Shiroma, Eric J, Sigurdsson, Sigurdur, Ghanbari, Mohsen, Boerwinkle, Eric, Fongang, Bernard, Wang, Ruiqi, Ikram, Mohammad K, Volker, Uwe, de Laat, Karlijn F, van Norden, Anouk GW, de Kort, Paul L, Vermeer, Sarah E, Brouwers, Paul JAM, Gons, Rob AR, den Heijer, Tom, van Dijk, Gert W, van Rooij, Frank GW, Aamodt, Anne H, Skogholt, Anne H, Willer, Cristen J, Heuch, Ingrid, Hagen, Knut, Fritsche, Lars G, Pedersen, Linda M, Ellekjaer, Hanne, Zhou, Wei, Martinsen, Amy E, Kristoffersen, Espen S, Thomas, Laurent F, Kleinschnitz, Christoph, Frantz, Stefan, Ungethum, Kathrin, Gallego-Fabrega, Cristina, Lledos, Miquel, Llucia-Carol, Laia, Sobrino, Tomas, Campos, Francisco, Castillo, Jose, Freijo, Marimar, Arenillas, Juan Francisco, Obach, Victor, Alvarez-Sabin, Jose, Molina, Carlos A, Ribo, Marc, Munoz-Narbona, Lucia, Lopez-Cancio, Elena, Millan, Monica, Diaz-Navarro, Rosa, Vives-Bauza, Cristofol, Serrano-Heras, Gemma, Segura, Tomas, Dhar, Rajat, Delgado-Mederos, Raquel, Prats-Sanchez, Luis, Camps-Renom, Pol, Blay, Natalia, Sumoy, Lauro, Marti-Fabregas, Joan, Schnohr, Peter, Jensen, Gorm B, Benn, Marianne, Afzal, Shoaib, Kamstrup, Pia R, van Setten, Jessica, van der Laan, Sander W, Vonk, Jet MJ, Kim, Bong-Jo, Curtze, Sami, Tiainen, Marjaana, Kinnunen, Janne, Menon, Vilas, Sung, Yun Ju, Yang, Chengran, Saillour-Glenisson, Florence, Gravel, Simon, Millwood, Iona Y, Gieger, Christian, Ninomiya, Toshiharu, Grabe, Hans J, Jukema, J Wouter, Rissanen, Ina L, Strbian, Daniel, Kim, Young Jin, Chen, Pei-Hsin, Mayerhofer, Ernst, Howson, Joanna MM, Adams, Hieab, Wassertheil-Smoller, Sylvia, Christensen, Kaare, Ikram, Mohammad A, Rundek, Tatjana, Worrall, Bradford B, Lathrop, G Mark, Riaz, Moeen, Simonsick, Eleanor M, Korv, Janika, Franca, Paulo HC, Zand, Ramin, Prasad, Kameshwar, Frikke-Schmidt, Ruth, Liman, Thomas, Haeusler, Karl Georg, Ruigrok, Ynte M, Heuschmann, Peter Ulrich, Longstreth, WT, Jung, Keum Ji, Bastarache, Lisa, Pare, Guillaume, Damrauer, Scott M, Chasman, Daniel I, Rotter, Jerome I, Zwart, John-Anker, Niiranen, Teemu J, Fornage, Myriam, Liaw, Yung-Po, Seshadri, Sudha, Fernandez-Cadenas, Israel, Walters, Robin G, Ruff, Christian T, Owolabi, Mayowa O, Huffman, Jennifer E, Milani, Lili, Kamatani, Yoichiro, Dichgans, Martin, and Debette, Stephanie

Abstract

Previous genome-wide association studies (GWASs) of stroke — the second leading cause of death worldwide — were conducted predominantly in populations of European ancestry1,2. Here, in cross-ancestry GWAS meta-analyses of 110,182 patients who have had a stroke (five ancestries, 33% non-European) and 1,503,898 control individuals, we identify association signals for stroke and its subtypes at 89 (61 new) independent loci: 60 in primary inverse-variance-weighted analyses and 29 in secondary meta-regression and multitrait analyses. On the basis of internal cross-ancestry validation and an independent follow-up in 89,084 additional cases of stroke (30% non-European) and 1,013,843 control individuals, 87% of the primary stroke risk loci and 60% of the secondary stroke risk loci were replicated (P < 0.05). Effect sizes were highly correlated across ancestries. Cross-ancestry fine-mapping, in silico mutagenesis analysis3, and transcriptome-wide and proteome-wide association analyses revealed putative causal genes (such as SH3PXD2A and FURIN) and variants (such as at GRK5 and NOS3). Using a three-pronged approach4, we provide genetic evidence for putative drug effects, highlighting F11, KLKB1, PROC, GP1BA, LAMC2 and VCAM1 as possible targets, with drugs already under investigation for stroke for F11 and PROC. A polygenic score integrating cross-ancestry and ancestry-specific stroke GWASs with vascular-risk factor GWASs (integrative polygenic scores) strongly predicted ischaemic stroke in populations of European, East Asian and African ancestry5. Stroke genetic risk scores were predictive of ischaemic stroke independent of clinical risk factors in 52,600 clinical-trial participants with cardiometabolic disease. Our results provide insights to inform biology, reveal potential drug targets and derive genetic risk prediction tools across ancestries.

Published
2022

33. Genome-wide transcriptome study in skin biopsies reveals an association of E2F4 with cadasil and cognitive impairment

Author

Instituto de Salud Carlos III, Fundació La Marató de TV3, European Commission, Cadasil, Agència de Gestió d'Ajuts Universitaris i de Recerca, Muiño, Elena, Maisterra, Olga, Jiménez-Balado, Joan, Cullell, Nàtalia, Carrera, Caty, Torres-Águila, Nuria P., Cárcel-Márquez, Jara, Gallego-Fabrega, Cristina, Lledós, Miquel, González-Sánchez, Jonathan, Olmos-Alpiste, Ferrán, Espejo, Eva, March, Álvaro, Pujol, Ramón, Rodríguez-Campello, Ana, Romeral, Gemma, Krupinski, Jurek, Marti-Fabregas, Joan, Montaner, Joan, Roquer, Jaume, Fernández-Cadenas, Israel, Instituto de Salud Carlos III, Fundació La Marató de TV3, European Commission, Cadasil, Agència de Gestió d'Ajuts Universitaris i de Recerca, Muiño, Elena, Maisterra, Olga, Jiménez-Balado, Joan, Cullell, Nàtalia, Carrera, Caty, Torres-Águila, Nuria P., Cárcel-Márquez, Jara, Gallego-Fabrega, Cristina, Lledós, Miquel, González-Sánchez, Jonathan, Olmos-Alpiste, Ferrán, Espejo, Eva, March, Álvaro, Pujol, Ramón, Rodríguez-Campello, Ana, Romeral, Gemma, Krupinski, Jurek, Marti-Fabregas, Joan, Montaner, Joan, Roquer, Jaume, and Fernández-Cadenas, Israel

Abstract

CADASIL is a small vessel disease caused by mutations in NOTCH3 that lead to an odd number of cysteines in the EGF-like repeat domain, causing protein misfolding and aggregation. The main symptoms are migraine, psychiatric disturbances, recurrent strokes and dementia, being executive function characteristically impaired. The molecular pathways altered by this receptor aggregation need to be studied further. A genome-wide transcriptome study (four cases paired with three healthy siblings) was carried out, in addition to a qRT-PCR for validation purposes (ten new cases and eight new controls). To study the expression profile by cell type of the significant mRNAs found, we performed an in situ hybridization (ISH) (nine cases and eight controls) and a research in the Single-nuclei Brain RNA-seq expression browser (SNBREB). Pathway analysis enrichment was carried out with Gene Ontology and Reactome. Neuropsychological tests were performed in five of the qRT-PCR cases. The two most significant differentially expressed mRNAs (BANP, p-value = 7.23 × 10–4 and PDCD6IP, p-value = 8.36 × 10–4) were selected for the validation study by qRT-PCR. Additionally, we selected two more mRNAs (CAMK2G, p-value = 4.52 × 10–3 and E2F4, p-value = 4.77 × 10–3) due to their association with ischemic neuronal death. E2F4 showed differential expression in the genome-wide transcriptome study and in the qRT-PCR (p = 1.23 × 10–3), and it was upregulated in CADASIL cases. Furthermore, higher E2F4 expression was associated with worse executive function (p = 2.04 × 10–2) and attention and information processing speed (IPS) (p = 8.73 × 10–2). In situ hibridization showed E2F4 expression in endothelial and vascular smooth vessel cells. In silico studies indicated that E2F4 is also expressed in brain endothelial cells. Among the most significant pathways analyzed, there was an enrichment of vascular development, cell adhesion and vesicular machinery terms and autophagy process. E2F4 is more highly expre

Published
2021

34. Development of imaging-based risk scores for prediction of intracranial haemorrhage and ischaemic stroke in patients taking antithrombotic therapy after ischaemic stroke or transient ischaemic attack: a pooled analysis of individual patient data from cohort studies

Author

Best, Jonathan G, primary, Ambler, Gareth, additional, Wilson, Duncan, additional, Lee, Keon-Joo, additional, Lim, Jae-Sung, additional, Shiozawa, Masayuki, additional, Koga, Masatoshi, additional, Li, Linxin, additional, Lovelock, Caroline, additional, Chabriat, Hugues, additional, Hennerici, Michael, additional, Wong, Yuen Kwun, additional, Mak, Henry Ka Fung, additional, Prats-Sanchez, Luis, additional, Martínez-Domeño, Alejandro, additional, Inamura, Shigeru, additional, Yoshifuji, Kazuhisa, additional, Arsava, Ethem Murat, additional, Horstmann, Solveig, additional, Purrucker, Jan, additional, Lam, Bonnie Yin Ka, additional, Wong, Adrian, additional, Kim, Young Dae, additional, Song, Tae-Jin, additional, Lemmens, Robin, additional, Eppinger, Sebastian, additional, Gattringer, Thomas, additional, Uysal, Ender, additional, Tanriverdi, Zeynep, additional, Bornstein, Natan M, additional, Ben Assayag, Einor, additional, Hallevi, Hen, additional, Molad, Jeremy, additional, Nishihara, Masashi, additional, Tanaka, Jun, additional, Coutts, Shelagh B, additional, Polymeris, Alexandros, additional, Wagner, Benjamin, additional, Seiffge, David J, additional, Lyrer, Philippe, additional, Algra, Ale, additional, Kappelle, L Jaap, additional, Al-Shahi Salman, Rustam, additional, Jäger, Hans R, additional, Lip, Gregory Y H, additional, Fischer, Urs, additional, El-Koussy, Marwan, additional, Mas, Jean-Louis, additional, Legrand, Laurence, additional, Karayiannis, Christopher, additional, Phan, Thanh, additional, Gunkel, Sarah, additional, Christ, Nicolas, additional, Abrigo, Jill, additional, Leung, Thomas, additional, Chu, Winnie, additional, Chappell, Francesca, additional, Makin, Stephen, additional, Hayden, Derek, additional, Williams, David J, additional, Mess, Werner H, additional, Nederkoorn, Paul J, additional, Barbato, Carmen, additional, Browning, Simone, additional, Wiegertjes, Kim, additional, Tuladhar, Anil M, additional, Maaijwee, Noortje, additional, Guevarra, Anne Cristine, additional, Yatawara, Chathuri, additional, Mendyk, Anne-Marie, additional, Delmaire, Christine, additional, Köhler, Sebastian, additional, van Oostenbrugge, Robert, additional, Zhou, Ying, additional, Xu, Chao, additional, Hilal, Saima, additional, Gyanwali, Bibek, additional, Chen, Christopher, additional, Lou, Min, additional, Staals, Julie, additional, Bordet, Régis, additional, Kandiah, Nagaendran, additional, de Leeuw, Frank-Erik, additional, Simister, Robert, additional, Hendrikse, Jeroen, additional, Kelly, Peter J, additional, Wardlaw, Joanna, additional, Soo, Yannie, additional, Fluri, Felix, additional, Srikanth, Velandai, additional, Calvet, David, additional, Jung, Simon, additional, Kwa, Vincent I H, additional, Engelter, Stefan T, additional, Peters, Nils, additional, Smith, Eric E, additional, Hara, Hideo, additional, Yakushiji, Yusuke, additional, Orken, Dilek Necioglu, additional, Fazekas, Franz, additional, Thijs, Vincent, additional, Heo, Ji Hoe, additional, Mok, Vincent, additional, Veltkamp, Roland, additional, Ay, Hakan, additional, Imaizumi, Toshio, additional, Gomez-Anson, Beatriz, additional, Lau, Kui Kai, additional, Jouvent, Eric, additional, Rothwell, Peter M, additional, Toyoda, Kazunori, additional, Bae, Hee-Joon, additional, Marti-Fabregas, Joan, additional, Werring, David J, additional, Harkness, Kirsty, additional, Shaw, Louise, additional, Sword, Jane, additional, Mohd Nor, Azlisham, additional, Sharma, Pankaj, additional, Kelly, Deborah, additional, Harrington, Frances, additional, Randall, Marc, additional, Smith, Matthew, additional, Mahawish, Karim, additional, Elmarim, Abduelbaset, additional, Esisi, Bernard, additional, Cullen, Claire, additional, Nallasivam, Arumug, additional, Price, Christopher, additional, Barry, Adrian, additional, Roffe, Christine, additional, Coyle, John, additional, Hassan, Ahamad, additional, Birns, Jonathan, additional, Cohen, David, additional, Sekaran, Lakshmanan, additional, Parry-Jones, Adrian, additional, Parry, Anthea, additional, Hargroves, David, additional, Proschel, Harald, additional, Datta, Prabel, additional, Darawil, Khaled, additional, Manoj, Aravindakshan, additional, Burn, Mathew, additional, Patterson, Chris, additional, Giallombardo, Elio, additional, Smyth, Nigel, additional, Mansoor, Syed, additional, Anwar, Ijaz, additional, Marsh, Rachel, additional, Ispoglou, Sissi, additional, Chadha, Dinesh, additional, Prabhakaran, Mathuri, additional, Meenakishundaram, Sanjeevikumar, additional, O'Connell, Janice, additional, Scott, Jon, additional, Krishnamurthy, Vinodh, additional, Aghoram, Prasanna, additional, McCormick, Michael, additional, Sprigg, Nikola, additional, O'Mahony, Paul, additional, Cooper, Martin, additional, Choy, Lillian, additional, Wilkinson, Peter, additional, Leach, Simon, additional, Caine, Sarah, additional, Burger, Ilse, additional, Gunathilagan, Gunaratam, additional, Guyler, Paul, additional, Emsley, Hedley, additional, Davis, Michelle, additional, Manawadu, Dulka, additional, Pasco, Kath, additional, Mamun, Maam, additional, Luder, Robert, additional, Sajid, Mahmud, additional, Okwera, James, additional, Warburton, Elizabeth, additional, Saastamoinen, Kari, additional, England, Timothy, additional, Putterill, Janet, additional, Flossman, Enrico, additional, Power, Michael, additional, Dani, Krishna, additional, Mangion, David, additional, Suman, Appu, additional, Corrigan, John, additional, Lawrence, Enas, additional, Vahidassr, Djamil, additional, Shakeshaft, Clare, additional, Brown, Martin, additional, Charidimou, Andreas, additional, Cohen, Hannah, additional, Banerjee, Gargi, additional, Houlden, Henry, additional, White, Mark, additional, Yousry, Tarek, additional, Flossmann, Enrico, additional, Muir, Keith, additional, Gratz, Pascal, additional, Mattle, Heinrich, additional, Panos, Leonidas, additional, Korczyn, Amos, additional, Kliper, Efrat, additional, Maeder, Philippe, additional, Gass, Achim, additional, Pachai, Chahin, additional, Bracoub, Luc, additional, Douste-Blazy, Marie-Yvonne, additional, Fratacci, Marie Dominique, additional, Vicaut, Eric, additional, Sato, Shoichiro, additional, Miwa, Kaori, additional, Fujita, Kyohei, additional, Ide, Toshihiro, additional, Ma, Henry, additional, Ly, John, additional, Singhal, Shaloo, additional, Chandra, Ronil, additional, Slater, Lee-Anne, additional, Soufan, Cathy, additional, Moran, Christopher, additional, Traenka, Christopher, additional, Thilemann, Sebastian, additional, Fladt, Joachim, additional, Gensicke, Henrik, additional, Bonati, Leo, additional, Kim, Beom Joon, additional, Han, Moon-Ku, additional, Kang, Jihoon, additional, Ko, Eunbin, additional, Yang, Mi Hwa, additional, Jang, Myung Suk, additional, Murphy, Sean, additional, Carty, Fiona, additional, Akijian, Layan, additional, Thornton, John, additional, Schembri, Mark, additional, Douven, Elles, additional, Delgado-Mederos, Raquel, additional, Marín, Rebeca, additional, Camps-Renom, Pol, additional, Guisado-Alonso, Daniel, additional, Nuñez, Fidel, additional, Medrano-Martorell, Santiago, additional, Merino, Elisa, additional, Iida, Kotaro, additional, Ikeda, Syuhei, additional, Irie, Hiroyuki, additional, Demirelli, Derya Selcuk, additional, Medanta, Jayesh Modi, additional, Zerna, Charlotte, additional, Hernández, Maria Valdés, additional, Armitage, Paul, additional, Heye, Anna, additional, Muñoz-Maniega, Susana, additional, Sakka, Eleni, additional, Thrippleton, Michael, additional, Dennis, Martin, additional, Beigneux, Ysoline, additional, Silva, Mauro, additional, Venketasubramanian, Narayanaswamy, additional, Ho, Shu Leung, additional, Cheung, Raymond Tak Fai, additional, Chan, Koon Ho, additional, Teo, Kay Cheong, additional, Hui, Edward, additional, Kwan, Joseph Shiu Kwong, additional, Chang, Richard, additional, Tse, Man Yu, additional, Hoi, Chu Peng, additional, Chan, Chung Yan, additional, Chan, Oi Ling, additional, Cheung, Ryan Hoi Kit, additional, Wong, Edmund Ka Ming, additional, Leung, Kam Tat, additional, Tsang, Suk Fung, additional, Ip, Hing Lung, additional, Ma, Sze Ho, additional, Ma, Karen, additional, Fong, Wing Chi, additional, Li, Siu Hung, additional, Li, Richard, additional, Ng, Ping Wing, additional, Wong, Kwok Kui, additional, Liu, Wenyan, additional, Wong, Lawrence, additional, Ramos, Lino, additional, De Schryver, Els, additional, Jöbsis, Joost, additional, van der Sande, Jaap, additional, Brouwers, Paul, additional, Roos, Yvo, additional, Stam, Jan, additional, Bakker, Stef, additional, Verbiest, Henk, additional, Schoonewille, Wouter, additional, Linn, Cisca, additional, Hertzberger, Leopold, additional, van Gemert, Maarten, additional, Berntsen, Paul, additional, Van Dam-Nolen, Dianne, additional, Kooi, M Eline, additional, Van der Lugt, Aad, additional, Koudstaal, Peter, additional, Leff, Alexander, additional, Ward, Nicholas, additional, Nachev, Parashkev, additional, Perry, Richard, additional, Ozkan, Hatice, additional, and Mitchell, John, additional

Published
2021
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35. Uric Acid Treatment After Stroke Prevents Long-Term Middle Cerebral Artery Remodelling and Attenuates Brain Damage in Spontaneously Hypertensive Rats

Author

Ministerio de Economía y Competitividad (España), Generalitat de Catalunya, Instituto de Salud Carlos III, European Commission, Jiménez-Altayó, Francesc [0000-0002-9034-2041], Jiménez-Xarrié, Elena, Pérez, Belén, Dantas, Ana Paula, Puertas-Umbert, Lídia, Marti-Fabregas, Joan, Chamorro, Ángel, Planas, Anna M., Vila, Elisabet, Jiménez-Altayó, Francesc, Ministerio de Economía y Competitividad (España), Generalitat de Catalunya, Instituto de Salud Carlos III, European Commission, Jiménez-Altayó, Francesc [0000-0002-9034-2041], Jiménez-Xarrié, Elena, Pérez, Belén, Dantas, Ana Paula, Puertas-Umbert, Lídia, Marti-Fabregas, Joan, Chamorro, Ángel, Planas, Anna M., Vila, Elisabet, and Jiménez-Altayó, Francesc

Abstract

Hypertension is the most important modifiable risk factor for stroke and is associated with poorer post-stroke outcomes. The antioxidant uric acid is protective in experimental normotensive ischaemic stroke. However, it is unknown whether this treatment exerts long-term protection in hypertension. We aimed to evaluate the impact of transient intraluminal middle cerebral artery (MCA) occlusion (90 min)/reperfusion (1–15 days) on brain and vascular damage progression in adult male Wistar-Kyoto (WKY; n = 36) and spontaneously hypertensive (SHR; n = 37) rats treated (i.v./120 min post-occlusion) with uric acid (16 mg kg−1) or vehicle (Locke’s buffer). Ischaemic brain damage was assessed longitudinally with magnetic resonance imaging and properties of MCA from both hemispheres were studied 15 days after stroke. Brain lesions in WKY rats were associated with a transitory increase in circulating IL-18 and cerebrovascular oxidative stress that did not culminate in long-term MCA alterations. In SHR rats, more severe brain damage and poorer neurofunctional outcomes were coupled to higher cortical cerebral blood flow at the onset of reperfusion, a transient increase in oxidative stress and long-lasting stroke-induced MCA hypertrophic remodelling. Thus, stroke promotes larger brain and vascular damage in hypertensive rats that persists for long-time. Uric acid administered during early reperfusion attenuated short- and long-term brain injuries in both normotensive and hypertensive rats, an effect that was associated with abolishment of the acute oxidative stress response and prevention of stroke-induced long-lasting MCA remodelling in hypertension. These results suggest that uric acid might be an effective strategy to improve stroke outcomes in hypertensive subjects.

Published
2020

36. Genome-Wide Association Study of VKORC1 and CYP2C9 on acenocoumarol dose, stroke recurrence and intracranial haemorrhage in Spain

Author

International Stroke Genetics Consortium, Consorcio español de genética del ictus, Redes Temáticas de Investigación Cooperativa en Salud (España), Cullell, Nàtalia, Carrera, Caty, Muiño, Elena, Torres-Águila, Nuria P., Cárcel-Márquez, Jara, González-Sánchez, Jonathan, Gallego-Fabrega, Cristina, Molina, Jessica, Besora, Sarah, Sotoca, Javier, Buongiorno, Maria Teresa, Jiménez-Conde, Jordi, Giralt-Steinhauer, Eva, Torres-Chacón, Reyes de, Montaner, Joan, Mancha, Fernando, Cabezas, Juan A., Marti-Fabregas, Joan, Prats-Sánchez, Luis, Camps-Renom, Pol, Purroy, Francisco, Cambray, Serafí, Freijo, Mar, Vives-Bauzá, Cristòfol, Tur, Sílvia, Font, Maria A., López-Cancio, Elena, Hernández-Pérez, María, Obach, Víctor, Calleja, Ana, Arenillas, Juan F., Rodríguez-Yáñez, Manuel, Castillo, José, Sobrino, Tomás, Fernández-Cadenas, Israel, Krupinski, Jerzy, International Stroke Genetics Consortium, Consorcio español de genética del ictus, Redes Temáticas de Investigación Cooperativa en Salud (España), Cullell, Nàtalia, Carrera, Caty, Muiño, Elena, Torres-Águila, Nuria P., Cárcel-Márquez, Jara, González-Sánchez, Jonathan, Gallego-Fabrega, Cristina, Molina, Jessica, Besora, Sarah, Sotoca, Javier, Buongiorno, Maria Teresa, Jiménez-Conde, Jordi, Giralt-Steinhauer, Eva, Torres-Chacón, Reyes de, Montaner, Joan, Mancha, Fernando, Cabezas, Juan A., Marti-Fabregas, Joan, Prats-Sánchez, Luis, Camps-Renom, Pol, Purroy, Francisco, Cambray, Serafí, Freijo, Mar, Vives-Bauzá, Cristòfol, Tur, Sílvia, Font, Maria A., López-Cancio, Elena, Hernández-Pérez, María, Obach, Víctor, Calleja, Ana, Arenillas, Juan F., Rodríguez-Yáñez, Manuel, Castillo, José, Sobrino, Tomás, Fernández-Cadenas, Israel, and Krupinski, Jerzy

Abstract

Acenocoumarol is an oral anticoagulant with significant interindividual dose variations. Variants in CYP2C9 and VKORC1 have been associated with acenocoumarol maintenance dose. We analysed whether any of the 49 polymorphisms in CYP2C9 and VKORC1 previously associated with acenocoumarol maintenance dose in a Genome-Wide Association study (GWAs) in Dutch population are associated with stroke recurrence, intracranial haemorrhage (ICH) and acenocoumarol maintenance dose in a Spanish population. We performed a GWAs using Human Core Exome-chip (Illumina) in 78 patients stroke patients treated with acenocoumarol for secondary prevention enrolled as part of the prospective investigator-initiated study (IIS) SEDMAN Study. Patients were followed-up a median of 12.8 months. Three and eight patients had recurrent stroke and ICH events, respectively. We found 14 of the 49 published variants associated with acenocoumarol maintenance dose (p < 0.05). Six polymorphisms were associated with stroke recurrence and four variants with ICH (p < 0.05). In conclusion, variants in VKORC1 and CYP2C9 are associated with acenocoumarol maintenance dose, stroke recurrence and ICH in a Spanish cohort. These results highlight the relevance of studying pharmacogenetics associated with efficacy and safety of anticoagulant drugs and justify studies with larger sample size and different ethnic populations.

Published
2020

37. Multi-ancestry genetic study in 5,876 patients identifies an association between excitotoxic genes and early outcomes after acute ischemic stroke

Author

Ibanez, Laura, primary, Heitsch, Laura, additional, Carrera, Caty, additional, Farias, Fabiana H.G., additional, Dhar, Rajat, additional, Budde, John, additional, Bergmann, Kristy, additional, Bradley, Joseph, additional, Harari, Oscar, additional, Phuah, Chia-Ling, additional, Lemmens, Robin, additional, Oliveira Souza, Alessandro A. Viana, additional, Moniche, Francisco, additional, Cabezas-Juan, Antonio, additional, Arenillas, Juan Francisco, additional, Krupinksi, Jerzy, additional, Cullell, Natalia, additional, Torres-Aguila, Nuria, additional, Muiño, Elena, additional, Cárcel-Márquez, Jara, additional, Marti-Fabregas, Joan, additional, Delgado-Mederos, Raquel, additional, Marin-Bueno, Rebeca, additional, Hornick, Alejandro, additional, Vives-Bauza, Cristofol, additional, Navarro, Rosa Diaz, additional, Tur, Silvia, additional, Jimenez, Carmen, additional, Obach, Victor, additional, Segura, Tomas, additional, Serrano-Heras, Gemma, additional, Chung, Jong-Won, additional, Roquer, Jaume, additional, Soriano-Tarraga, Carol, additional, Giralt-Steinhauer, Eva, additional, Mola-Caminal, Marina, additional, Pera, Joanna, additional, Lapicka-Bodzioch, Katarzyna, additional, Derbisz, Justyna, additional, Davalos, Antoni, additional, Lopez-Cancio, Elena, additional, Muñoz, Lucia, additional, Tatlisumak, Turgut, additional, Molina, Carlos, additional, Ribo, Marc, additional, Bustamante, Alejandro, additional, Sobrino, Tomas, additional, Castillo-Sanchez, Jose, additional, Campos, Francisco, additional, Rodriguez-Castro, Emilio, additional, Arias-Rivas, Susana, additional, Rodríguez-Yáñez, Manuel, additional, Herbosa, Christina, additional, Ford, Andria L., additional, Arauz, Antonio, additional, Lopes-Cendes, Iscia, additional, Lowenkopf, Theodore, additional, Barboza, Miguel A., additional, Amini, Hajar, additional, Stamova, Boryana, additional, Ander, Bradley P., additional, Sharp, Frank R, additional, Kim, Gyeong Moon, additional, Bang, Oh Young, additional, Jimenez-Conde, Jordi, additional, Slowik, Agnieszka, additional, Stribian, Daniel, additional, Tsai, Ellen A., additional, Burkly, Linda C., additional, Montaner, Joan, additional, Fernandez-Cadenas, Israel, additional, Lee, Jin-Moo, additional, and Cruchaga, Carlos, additional

Published
2020
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38. A Genome-Wide Meta-Analysis

Author

Mola-Caminal, Marina, Carrera, Caty, Soriano-Tárraga, Carolina, Giralt-Steinhauer, Eva, Díaz-Navarro, Rosa M., Tur, Sílvia, Jiménez, Carmen, Medina-Dols, Aina, Cullell, Nàtalia, Torres-Águila, Nuria P., Muiño, Elena, Rodríguez-Campello, Ana, Ois, Ángel, Cuadrado-Godia, Elisa, Vivanco-Hidalgo, Rosa M., Hernández-Guillamón, Mar, Solé, Montse, Delgado, Pilar, Bustamante, Alejandro, García-Berrocoso, Teresa, Mendióroz, Maite, Castellanos, Mar, Serena, Joaquín, Marti-Fabregas, Joan, Segura, Tomás, Serrano-Heras, Gemma, Obach, Víctor, Ribó, Marc, Molina, Carlos A., Álvarez-Sabín, José, Palomeras, Ernest, Freijo, Mar, Font, Maria A., Rosand, Jonathan, Rost, Natalia S., Gallego-Fabrega, Cristina, Lee, Jin-Moo, Heitsch, Laura, Ibáñez, Laura, Cruchaga, Carlos, Phuah, Chia-Ling, Lemmens, Robin, Thijs, Vincent, Lindgren, Arne, Maguire, Jane, Rannikmae, Kistiina, Sudlow, Catherine L., Jern, Christina, Stanne, Tara M., Lorentzen, Erik, Muñoz-Narbona, Lucía, Dávalos, Antonio, López-Cancio, Elena, Worrall, Bradford B., Woo, Daniel, Kittner, Steven J., Mitchell, Braxton D., Montaner, Joan, Roquer, Jaume, Krupinski, Jurek, Estivill, Xavier, Rabionet, Raquel, Vives-Bauzá, Cristòfol, Fernández-Cadenas, Israel, Jiménez-Conde, Jordi, Fundació La Marató de TV3, Instituto de Salud Carlos III, National Institutes of Health (US), and National Institute of Neurological Disorders and Stroke (US)

Subjects
Allele, Genome-wide association study, Ischemic stroke, Genetic loci, cardiovascular diseases, Genetic variant
Abstract

[Rationale] Ischemic stroke is among the leading causes of adult disability. Part of the variability in functional outcome after stroke has been attributed to genetic factors but no locus has been consistently associated with stroke outcome., [Objective] Our aim was to identify genetic loci influencing the recovery process using accurate phenotyping to produce the largest GWAS (genome-wide association study) in ischemic stroke recovery to date., [Methods and Results] A 12-cohort, 2-phase (discovery-replication and joint) meta-analysis of GWAS included anterior-territory and previously independent ischemic stroke cases. Functional outcome was recorded using 3-month modified Rankin Scale. Analyses were adjusted for confounders such as discharge National Institutes of Health Stroke Scale. A gene-based burden test was performed. The discovery phase (n=1225) was followed by open (n=2482) and stringent joint-analyses (n=1791). Those cohorts with modified Rankin Scale recorded at time points other than 3-month or incomplete data on previous functional status were excluded in the stringent analyses. Novel variants in PATJ (Pals1-associated tight junction) gene were associated with worse functional outcome at 3-month after stroke. The top variant was rs76221407 (G allele, β=0.40, P=1.70×10−9)., [Conclusions] Our results identify a set of common variants in PATJ gene associated with 3-month functional outcome at genome-wide significance level. Future studies should examine the role of PATJ in stroke recovery and consider stringent phenotyping to enrich the information captured to unveil additional stroke outcome loci., Genetic contribution to functional outcome and disability after stroke (GODS) project, Fundació Marató-TV3 Grant 2011 (76/C/2011), Recercaixa’13; Generación Project, Instituto de Salud Carlos III; GENISIS (Genetics of Early Neurological InStability After Ischemic Stroke) project, National Institutes of Health (NIH); National Institute of Neurological Disorders and Stroke Stroke Genetics Network (SiGN) Project, NIH.

Published
2019

39. Consensus statements and recommendations from the ESO-Karolinska Stroke Update Conference, Stockholm 11-13 November 2018

Author

Ahmed, Niaz Audebert, Heinrich Turc, Guillaume Cordonnier, Charlotte Christensen, Hanne Sacco, Simona Sandset, Else Charlotte Ntaios, George Charidimou, Andreas Toni, Danilo and Pristipino, Christian Koehrmann, Martin Kuramatsu, Joji B. and Thomalla, Geotz Mikulik, Robert Ford, Gary A. and Marti-Fabregas, Joan Fischer, Urs Thoren, Magnus Lundstrom, Erik Rinkel, Gabriel J. E. van der Worp, H. Bart and Matusevicius, Marius Tsivgoulis, Georgios Milionis, Haralampos and Rubiera, Marta Hart, Robert Moreira, Tiago Lantz, Maria and Sjostrand, Christina Andersen, Grethe Schellinger, Peter and Kostulas, Konstantinos Sunnerhagen, Katharina Stibrant Keselman, Boris Korompoki, Eleni Purrucker, Jan Khatri, Pooja and Whiteley, William Berge, Eivind Mazya, Michael Dippel, Diederik W. J. Mustanoja, Satu Rasmussen, Mads Soderqvist, Asa Kuntze Escudero-Martinez, Irene Steiner, Thorsten

Abstract

The purpose of the European Stroke Organisation-Karolinska Stroke Update Conference is to provide updates on recent stroke therapy research and to give an opportunity for the participants to discuss how these results may be implemented into clinical routine. The meeting started 22 years ago as Karolinska Stroke Update, but since 2014 it is a joint conference with European Stroke Organisation. Importantly, it provides a platform for discussion on the European Stroke Organisation guidelines process and on recommendations to the European Stroke Organisation guidelines committee on specific topics. By this, it adds a direct influence from stroke professionals otherwise not involved in committees and work groups on the guideline procedure. The discussions at the conference may also inspire new guidelines when motivated. The topics raised at the meeting are selected by the scientific programme committee mainly based on recent important scientific publications. This year's European Stroke Organisation-Karolinska Stroke Update Meeting was held in Stockholm on 11-13 November 2018. There were 11 scientific sessions discussed in the meeting including two short sessions. Each session except the short sessions produced a consensus statement (Full version with background, issues, conclusions and references are published as web-material and at and ) and recommendations which were prepared by a writing committee consisting of session chair(s), scientific secretary and speakers. These statements were presented to the 250 participants of the meeting. In the open meeting, general participants commented on the consensus statement and recommendations and the final document were adjusted based on the discussion from the general participants Recommendations (grade of evidence) were graded according to the 1998 Karolinska Stroke Update meeting with regard to the strength of evidence. Grade A Evidence: Strong support from randomised controlled trials and statistical reviews (at least one randomised controlled trial plus one statistical review). Grade B Evidence: Support from randomised controlled trials and statistical reviews (one randomised controlled trial or one statistical review). Grade C Evidence: No reasonable support from randomised controlled trials, recommendations based on small randomised and/or non-randomised controlled trials evidence.

Published
2019

40. Efficacy and Safety of Rivaroxaban Versus Aspirin in Embolic Stroke of Undetermined Source and Carotid Atherosclerosis

Author

Ntaios, George Swaminathan, Balakumar Berkowitz, Scott D. and Gagliardi, Rubens Jose Lang, Wilfried Siegler, James E. and Lavados, Pablo Mundl, Hardi Bornstein, Natan Meseguer, Elena and Amarenco, Pierre Cucchiara, Brett Camps-Renom, Pol and Makaritsis, Konstantinos Korompoki, Eleni Papavasileiou, Vasileios Marti-Fabregas, Joan Milionis, Haralampos Vemmos, Konstantinos Connolly, Stuart J. Hart, Robert G. NAVIGATE ESUS Investigators

Subjects
cardiovascular diseases
Abstract

Background and Purpose- The sources of emboli in patients with embolic stroke of undetermined source (ESUS) are multiple and may not respond uniformly to anticoagulation. In this exploratory subgroup analysis of patients with carotid atherosclerosis in the NAVIGATE (New Approach Rivaroxaban Inhibition of Factor Xa in a Global Trial Versus ASA to Prevent Embolism)-ESUS trial, we assessed whether the treatment effect in this subgroup is consistent with the overall trial population and investigated the association of carotid atherosclerosis with recurrent ischemic stroke. Methods- Carotid atherosclerosis was analyzed either as the presence of mild (ie, 20%-49%) atherosclerotic stenosis or, separately, as the presence of carotid plaque. Primary efficacy outcome was ischemic stroke recurrence. Safety outcomes were major bleeding and symptomatic intracerebral bleeding. Results- Carotid plaque was present in 40% of participants and mild carotid stenosis in 11%. There was no significant difference in ischemic stroke recurrence between rivaroxaban- and aspirin-treated patients among 490 patients with carotid stenosis (5.0 versus 5.9/100 patient-years, respectively, hazard ratio [HR], 0.85; 95% CI, 0.39-1.87; P for interaction of treatment effect with patients without carotid stenosis 0.78) and among 2905 patients with carotid plaques (5.9 versus 4.9/100 patient-years, respectively, HR, 1.20; 95% CI, 0.86-1.68; P for interaction of treatment effect with patients without carotid stenosis 0.2). Among patients with carotid plaque, major bleeding was more frequent in rivaroxaban-treated patients compared with aspirin-treated (2.0 versus 0.5/100 patient-years, HR, 3.75; 95% CI, 1.63-8.65). Patients with carotid stenosis had similar rate of ischemic stroke recurrence compared with those without (5.4 versus 4.9/100 patient-years, respectively, HR, 1.11; 95% CI, 0.73-1.69), but there was a strong trend of higher rate of ischemic stroke recurrence in patients with carotid plaque compared with those without (5.4 versus 4.3/100 patient-years, respectively, HR, 1.23; 95% CI, 0.99-1.54). Conclusions- In ESUS patients with carotid atherosclerosis, we found no difference in efficacy between rivaroxaban and aspirin for prevention of recurrent stroke, but aspirin was safer, consistent with the overall trial results. Carotid plaque was much more often present ipsilateral to the qualifying ischemic stroke than contralateral, supporting an important etiological role of nonstenotic carotid disease in ESUS.

Published
2019

41. A Genome-Wide Meta-Analysis

Author

Mola-Caminal, Marina, Carrera, Caty, Soriano-Tárraga, Carolina, Giralt-Steinhauer, Eva, Díaz-Navarro, Rosa M., Tur, Sílvia, Jiménez, Carmen, Medina-Dols, Aina, Cullell, Nàtalia, Torres-Águila, Nuria P., Muiño, Elena, Rodríguez-Campello, Ana, Ois, Ángel, Cuadrado-Godia, Elisa, Vivanco-Hidalgo, Rosa M., Hernández-Guillamón, Mar, Solé, Montse, Delgado, Pilar, Bustamante, Alejandro, García-Berrocoso, Teresa, Mendióroz, Maite, Castellanos, Mar, Serena, Joaquín, Marti-Fabregas, Joan, Segura, Tomás, Serrano-Heras, Gemma, Obach, Víctor, Ribó, Marc, Molina, Carlos A., Álvarez-Sabín, José, Palomeras, Ernest, Freijo, Mar, Font, Maria A., Rosand, Jonathan, Rost, Natalia S., Gallego-Fabrega, Cristina, Lee, Jin-Moo, Heitsch, Laura, Ibáñez, Laura, Cruchaga, Carlos, Phuah, Chia-Ling, Lemmens, Robin, Thijs, Vincent, Lindgren, Arne, Maguire, Jane, Rannikmae, Kistiina, Sudlow, Catherine L., Jern, Christina, Stanne, Tara M., Lorentzen, Erik, Muñoz-Narbona, Lucía, Dávalos, Antonio, López-Cancio, Elena, Worrall, Bradford B., Woo, Daniel, Kittner, Steven J., Mitchell, Braxton D., Montaner, Joan, Roquer, Jaume, Krupinski, Jurek, Estivill, Xavier, Rabionet, Raquel, Vives-Bauzá, Cristòfol, Fernández-Cadenas, Israel, Jiménez-Conde, Jordi, Fundació La Marató de TV3, Instituto de Salud Carlos III, National Institutes of Health (US), and National Institute of Neurological Disorders and Stroke (US)

Subjects
genetic variant, genome-wide association study, Tight Junction Proteins, allele, Stroke Rehabilitation, genetic loci, Recovery of Function, Polymorphism, Single Nucleotide, Brain Ischemia, Stroke, Disability Evaluation, Phenotype, Treatment Outcome, Gene Frequency, Risk Factors, ischemic stroke, Humans, Genetic Predisposition to Disease, Genome-Wide Association Study
Abstract

[Rationale] Ischemic stroke is among the leading causes of adult disability. Part of the variability in functional outcome after stroke has been attributed to genetic factors but no locus has been consistently associated with stroke outcome. [Objective] Our aim was to identify genetic loci influencing the recovery process using accurate phenotyping to produce the largest GWAS (genome-wide association study) in ischemic stroke recovery to date. [Methods and Results] A 12-cohort, 2-phase (discovery-replication and joint) meta-analysis of GWAS included anterior-territory and previously independent ischemic stroke cases. Functional outcome was recorded using 3-month modified Rankin Scale. Analyses were adjusted for confounders such as discharge National Institutes of Health Stroke Scale. A gene-based burden test was performed. The discovery phase (n=1225) was followed by open (n=2482) and stringent joint-analyses (n=1791). Those cohorts with modified Rankin Scale recorded at time points other than 3-month or incomplete data on previous functional status were excluded in the stringent analyses. Novel variants in PATJ (Pals1-associated tight junction) gene were associated with worse functional outcome at 3-month after stroke. The top variant was rs76221407 (G allele, β=0.40, P=1.70×10−9). [Conclusions] Our results identify a set of common variants in PATJ gene associated with 3-month functional outcome at genome-wide significance level. Future studies should examine the role of PATJ in stroke recovery and consider stringent phenotyping to enrich the information captured to unveil additional stroke outcome loci. Genetic contribution to functional outcome and disability after stroke (GODS) project, Fundació Marató-TV3 Grant 2011 (76/C/2011), Recercaixa’13; Generación Project, Instituto de Salud Carlos III; GENISIS (Genetics of Early Neurological InStability After Ischemic Stroke) project, National Institutes of Health (NIH); National Institute of Neurological Disorders and Stroke Stroke Genetics Network (SiGN) Project, NIH.

Published
2018

43. Clinical Variables and Genetic Risk Factors Associated with the Acute Outcome of Ischemic Stroke: A Systematic Review

Author

Instituto de Salud Carlos III, Torres-Águila, Nuria P., Carrera, Caty, Muiño, Elena, Cullell, Nàtalia, Cárcel-Márquez, Jara, Gallego-Fabrega, Cristina, González-Sánchez, Jonathan, Bustamante, Alejandro, Delgado, Pilar, Ibáñez, Laura, Heitsch, Laura, Krupinski, Jerzy, Montaner, Joan, Marti-Fabregas, Joan, Cruchaga, Carlos, Lee, Jin-Moo, Fernández-Cadenas, Israel, Instituto de Salud Carlos III, Torres-Águila, Nuria P., Carrera, Caty, Muiño, Elena, Cullell, Nàtalia, Cárcel-Márquez, Jara, Gallego-Fabrega, Cristina, González-Sánchez, Jonathan, Bustamante, Alejandro, Delgado, Pilar, Ibáñez, Laura, Heitsch, Laura, Krupinski, Jerzy, Montaner, Joan, Marti-Fabregas, Joan, Cruchaga, Carlos, Lee, Jin-Moo, and Fernández-Cadenas, Israel

Abstract

Stroke is a complex disease and one of the main causes of morbidity and mortality among the adult population. A huge variety of factors is known to influence patient outcome, including demographic variables, comorbidities or genetics. In this review, we expound what is known about the influence of clinical variables and related genetic risk factors on ischemic stroke outcome, focusing on acute and subacute outcome (within 24 to 48 hours after stroke and until day 10, respectively), as they are the first indicators of stroke damage. We searched the PubMed data base for articles that investigated the interaction between clinical variables or genetic factors and acute or subacute stroke outcome. A total of 61 studies were finally included in this review. Regarding the data collected, the variables consistently associated with acute stroke outcome are: glucose levels, blood pressure, presence of atrial fibrillation, prior statin treatment, stroke severity, type of acute treatment performed, severe neurological complications, leukocyte levels, and genetic risk factors. Further research and international efforts are required in this field, which should include genome-wide association studies.

Published
2019

44. Genome-Wide Association Study of White Blood Cell Counts in Patients With Ischemic Stroke

Author

Torres-Águila, Nuria P., Carrera, Caty, Giese, Anne-Katrine, Cullell, Nàtalia, Muiño, Elena, Cárcel-Márquez, Jara, Gallego-Fabrega, Cristina, González-Sánchez, Jonathan, Freijo, Mar, Álvarez-Sabín, José, Molina, Carlos A., Ribó, Marc, Jiménez-Conde, Jordi, Roquer, Jaume, Sobrino, Tomás, Campos-Rodríguez, Francisco, Castillo, José, Muñoz-Narbona, Lucía, López-Cancio, Elena, Dávalos, Antonio, Díaz-Navarro, Rosa M., Tur, Sílvia, Vives-Bauzá, Cristòfol, Serrano-Heras, Gemma, Segura, Tomás, Krupinski, Jerzy, Delgado-Mederos, Raquel, Marti-Fabregas, Joan, Heitsch, Laura, Ibáñez, Laura, Cruchaga, Carlos, Rost, Natalia S., Montaner, Joan, Torres-Águila, Nuria P., Carrera, Caty, Giese, Anne-Katrine, Cullell, Nàtalia, Muiño, Elena, Cárcel-Márquez, Jara, Gallego-Fabrega, Cristina, González-Sánchez, Jonathan, Freijo, Mar, Álvarez-Sabín, José, Molina, Carlos A., Ribó, Marc, Jiménez-Conde, Jordi, Roquer, Jaume, Sobrino, Tomás, Campos-Rodríguez, Francisco, Castillo, José, Muñoz-Narbona, Lucía, López-Cancio, Elena, Dávalos, Antonio, Díaz-Navarro, Rosa M., Tur, Sílvia, Vives-Bauzá, Cristòfol, Serrano-Heras, Gemma, Segura, Tomás, Krupinski, Jerzy, Delgado-Mederos, Raquel, Marti-Fabregas, Joan, Heitsch, Laura, Ibáñez, Laura, Cruchaga, Carlos, Rost, Natalia S., and Montaner, Joan

Abstract

[Background and Purpose] Immune cells play a key role in the first 24h poststroke (acute phase), being associated with stroke outcome. We aimed to find genetic risk factors associated with leukocyte counts during the acute phase of stroke., [Methods] Ischemic stroke patients with leukocyte counts data during the first 24h were included. Genome-wide association study and gene expression studies were performed., [Results] Our genome-wide association study, which included 2064 (Discovery) and 407 (Replication) patients, revealed a new locus (14q24.3) associated with leukocyte counts. After Joint analysis (n=2471) 5 more polymorphisms reached genome-wide significance (P<5×10−8). The 14q24.3 locus was associated with acute stroke outcome (rs112809786, P=0.036) and with ACOT1 and PTGR2 gene expression. Previous polymorphisms associated with leukocyte counts in general-population did not show any significance in our study., [Conclusions] We have found the first locus associated with leukocyte counts in ischemic stroke, also associated with acute outcome. Genetic analysis of acute endophenotypes could be useful to find the genetic factors associated with stroke outcome. Our findings suggested a different modulation of immune cells in stroke compared with healthy conditions.

Published
2019

47. Sphenopalatine Ganglion Stimulation to Augment Cerebral Blood Flow

Author

Bornstein, Natan M., primary, Saver, Jeffrey L., additional, Diener, Hans-Christoph, additional, Gorelick, Philip B., additional, Shuaib, Ashfaq, additional, Solberg, Yoram, additional, Devlin, Thomas, additional, Leung, Thomas, additional, Molina, Carlos A., additional, Skoloudik, David, additional, Fiksa, Jan, additional, Krieger, Derk, additional, Andersen, Grethe, additional, Berrouschot, Joerg, additional, Hobohm, Carsten, additional, Schneider, Dietmar, additional, Griewing, Bernd, additional, Endres, Matthias, additional, Hausler, Karl-Georg, additional, Kimmig, Hubert, additional, Ringleb, Peter, additional, Weimar, Christian, additional, Schilling, Matthias, additional, Kohrmann, Martin, additional, Hetzel, Andreas, additional, Kaps, Manfred, additional, Cheung, Raymond, additional, Sobolewski, Piotr, additional, Nyke, Walenty, additional, Czlonkowska, Anna, additional, Stepien, Adam, additional, Waldemar, Brola, additional, Słowik, Agnieszka, additional, Zbigniewem, Stelmasiakiem, additional, Lubiński, Ignacy, additional, Portela, Pedro, additional, Segure, Tomas, additional, Marti-Fabregas, Joan, additional, Alonso, Maria, additional, Nunez, Antonio, additional, Miguel, Miguel Blanco, additional, Campello, Anna, additional, Arenillas, Joaquin, additional, Marshall, Nash, additional, Chiu, David, additional, Shownkeen, Harish, additional, Rymer, Marilyn, additional, Sen, Souvik, additional, Roubec, Martin, additional, Kuliha, Martin, additional, Lakomý, Ctirad, additional, Tyl, David, additional, Kemlink, David, additional, Doležal, Ondřej, additional, Rekova, Petra, additional, Krejčí, Veronika, additional, Christensen, Anders, additional, Belhage, Bo, additional, Maschmann, Christian, additional, Kruse Larsen, Christian, additional, Pott, Frank, additional, Christensen, Hanne, additional, Marstrand, Jakob, additional, Nielsen, Jens Kjellberg, additional, Meden, Per, additional, Prytz, Svend, additional, Rosenbaum, Sverre, additional, Hedemann Sorensen, Jens Christian, additional, Stenhoj Meier, Kaare, additional, Schmift Ettrup, Kare, additional, Dupont Hougaard, Kristina, additional, Von Wietzel, Paul, additional, Stoll, Anett, additional, Schwetlick, Hans, additional, Pradel, Hendirk, additional, Hemprich, Alexander, additional, Schulz, Andreas, additional, Frerich, Bernhard, additional, Weise, Christopher, additional, Michalski, Dominik, additional, Schaller, Felix, additional, Schiefke, Franziska, additional, Helmrich, Jens, additional, Pelz, Johann, additional, Schnieder, Martin, additional, Schneider, Martin, additional, Matzen, Peter, additional, Langos, Rudiger, additional, Müller-Duerwald, Stephan, additional, Lukhaup, Sven, additional, Bauer, Ute, additional, Kloppig, Wolfgang, additional, Hiermann, Erich, additional, Mucha, Gregor, additional, Soda, Hassan, additional, Weinhardt, Renate, additional, Mucha, Teresa, additional, Ziegler, Volker, additional, Abbushi, Alexander, additional, Hotter, Benjamin, additional, Winter, Benjamin, additional, Anthofer, Birgit, additional, Noack, Cornelia, additional, Laubisch, Dinah, additional, Heldge Schneider, Gerd, additional, Jan Jungehulsing, Gerhard, additional, Mueller, Heiko, additional, Dreier, Jens, additional, Fiebach, Jochen, additional, Flechsenhar, Julia, additional, Villringer, Kersten, additional, Ebinger, Martin, additional, Rozanski, Michael, additional, Vajkoczy, Peter, additional, Klingebiel, Randolf, additional, Steinicke, Robert, additional, Pittl, Sandra, additional, Hoffmann, Sarah, additional, Maul, Stephan, additional, Krause, Thomas, additional, Liman, Thomas, additional, Plath, Thomas, additional, Nowe, Tim, additional, Schmidt, Wolf, additional, Fritzsch, Carsten, additional, Haas, Christopher, additional, Will, Hans-Gerd, additional, Haußmann-Betz, Katja, additional, Bayat, Mohsen, additional, Pordzik, Tomazs, additional, Hug, Andreas, additional, Staff, Christian Jürgen, additional, Lichy, Christoph, additional, Eggers, Georg, additional, Kloss, Manja, additional, Bendszus, Martin, additional, Herrmann, Oliver, additional, Seeberger, Robin, additional, Schwarting, Soenke, additional, Rhode, Stefan, additional, Rizos, Timolaos, additional, Hacke, Werner, additional, Frank, Benedikt, additional, Bozkurt, Bessi, additional, Holle, Dagny, additional, Mueller, Daniel, additional, Koch, Dirk, additional, Shanib, Hind, additional, Sudendey, Joachim, additional, Brenck, Johannes, additional, Busch, Kolja, additional, Gartzen, Kristina, additional, Gasser, Thomas, additional, Hagenacker, Tim, additional, Buerke, Boris, additional, Prigge, Gudrun, additional, Minnerup, Jens, additional, Albers, Johannes, additional, Wermker, Kai, additional, Schwindt, Wolfram, additional, Kallmünzer, Ringlestein, Bernd, additional, Hauer, Eva, additional, Breuer, Lorenz, additional, Schellinger, Peter, additional, Kollmar, Rainer, additional, Sauer, Roland, additional, Schwab, Stefan, additional, Struffert, Tobias, additional, Funfack, Anette, additional, Stechmann, Anne, additional, Schlaeger, Axel, additional, Laeppchen, Claus, additional, Schuchardt, Florian, additional, Klingler, Jan-Helge, additional, Reis, Janine, additional, Lambeck, Johann, additional, Friedrich, Mirko, additional, Laible, Mona, additional, Wellermeyer, Philip, additional, Beck, Sandra, additional, Rutsch, Sebastian, additional, Niesen, Wolf-Dirk, additional, Tanislav, Christian, additional, Schaaf, Heidrun, additional, Kerkmann, Heiko, additional, Schirotzek, Ingo, additional, Allendörfer, Jens, additional, Wolff, Stephanie, additional, Yuk-Lun Lau, Alexander, additional, Yin Yan Chan, Anne, additional, Siu, Deyond, additional, Wong, Edward HC, additional, Chu Wong, George Kwok, additional, Leung, Howan, additional, Wong, Lawrence K.S., additional, Zhu, Xian Lun, additional, Yan Soo, Yannie Oi, additional, Ting Tse, Alan Choi, additional, Kit Leung, Gilberto Ka, additional, Leung, Kar Ming, additional, Ngai Hung, Kwan, additional, Wai Mei Kwan, May, additional, Man Yu Tse, Mona, additional, Tse, Philip, additional, Hon Chan, Ping, additional, Lee, Raymand, additional, Shek Kwan Chang, Richard, additional, Yin Yu Pang, Shirley, additional, Fong Kwong Hon, Sonny, additional, Cheng, Tat Sun, additional, Lui, Wai Man, additional, Wo Mak, Windsor Wai, additional, Sobota, Anna, additional, Wiater, Baeta, additional, Loch, Barbara, additional, Wolak, Genowefa, additional, Łabudzka, Irena, additional, Dabal, Jan, additional, Grzesik, Marcin, additional, Sledzinska, Monika, additional, Hatalska-Żerebiec, Renata, additional, Szczuchniak, Wiktor, additional, Gójska, Anna, additional, Nałęcz, Dariusz, additional, Gasecki, Dariusz, additional, Kozera, Grzegorz, additional, Dylewicz, Łukasz, additional, Niekra, Marcin, additional, Kwarciany, Mariusz, additional, Chomik, Piotr, additional, Skowron, Piotr, additional, Kobayashi, Adam, additional, Chabik, Grzegorz, additional, Makowicz, Grzegorz, additional, Bembenek, Jan, additional, Jędrzejewska, Julia, additional, Karlinski, Michal, additional, Czepiel, Wojciech, additional, Brodacki, Bogdan, additional, Staszewski, Jacek, additional, Kosek, Jarosław, additional, Jadczak, Marcin, additional, Durka-Kęsy, Marta, additional, Kaluzny, Krzysztof, additional, Ziomek, Małgorzata, additional, Fudala, Małgorzata, additional, Sosnowski, Zbigniew, additional, Ferens, Antoni, additional, Szczygieł, Elżbieta, additional, Banaszkiewicz, Krzysztof, additional, Ziomek, Maciej, additional, Wnuk, Marcin, additional, Szczepańska-Szerej, Anna, additional, Jach, Ewa, additional, Maslanko, Grazyna Elzbieta, additional, Wojczal, Joanna, additional, Luchowski, Piotr, additional, Kowalczyk, Andrzej, additional, Jakubiak, Jerzy, additional, Kopcewicz, Joanna, additional, Gajda, Maciej, additional, Wichlinska-Lubinska, Malgorzata, additional, Rodriguez, David, additional, Santamarin, Estevo, additional, Pagola, Jorge, additional, Lorente Guerrero, Juan, additional, Ribo, Marc, additional, Rubiera, Marta, additional, Maisterra, Olga, additional, Pinero, Soccoro, additional, Catalina Iglesias, Valera, additional, Plans, Gerard, additional, Quesada, Helena, additional, Aparicio Caballero, Marco Alberto, additional, Portela, Pedro Cardona, additional, De Diego, Antonio Belinchon, additional, Garay, David Sopelana, additional, García Rodriguez, Máximo Rafael, additional, Martin, Oscar Ayo, additional, Braña, Silvia Crusat, additional, Garcia, Jorge, additional, Hernandez, Fernando Munoz, additional, Catala, Ignasi, additional, Marti-Vilalta, Josep Lluis, additional, Delgado Mederos, Rachel, additional, de Quintana, Schmid Cristian, additional, Martinez-Ramirez, Sergi, additional, Valcarcel Gonzalez, Jaime, additional, Masjuan Vallejo, Jaime, additional, Diamantopoulus, Jorge, additional, Del Alamo, Marta, additional, Poveda, Pedro Domingo, additional, Pastor, Andres Garcia, additional, Carballal, Calros Fernandez, additional, Diaz, Fernando, additional, Garcia Leal, Roberto, additional, Juretschke, Ruiz, additional, Echabe, Eduardo Arán, additional, Sanchez, Jose Castillo, additional, Yanez, Manuel Rodriguez, additional, Garcia, Ramon Serramito, additional, Muino, Rogelio Leira, additional, Rivas, Susana Arias, additional, Lopez Gonzalez, Demian Manzano, additional, Cuadrado, Elisa, additional, Giralt, Eva, additional, Villalba, Gloria, additional, Roquer, Jaime, additional, Angel, Ois, additional, Jimenez, Maria, additional, Cedeño, René Robles, additional, Salinas, Ruy, additional, Lejarreta, Saioa, additional, Silva, Yolanda, additional, Fraile, Adela, additional, Calleja, Ana, additional, Cepeda Landínez, Guillermo Arturo, additional, Tellez, Nieves, additional, Garcia Bermejo, Pablo, additional, Santos, Pérez Jaime, additional, Herranz, Rosa Fernandez, additional, Hunt, Peter, additional, Browning, Donald, additional, Violette, Michael, additional, Hoddeson, Robert, additional, Rose, James, additional, Zhang, Jonathan, additional, Mazumdar, Avi, additional, Echiverri, Henri, additional, Chow, James, additional, Lovick, Darren, additional, Coleman, Martin, additional, Akhtar, Naveed, additional, Sugg, Rebecca, additional, Zanation, Adam, additional, Germanwala, Anand, additional, Senior, Brent, additional, Huang, David, additional, Aucutt-Walter, Natalie, additional, Kasner, Scott, additional, LeRoux, Peter, additional, von Kummer, Rüdiger, additional, and Palesch, Yuko, additional

Published
2019
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48. An injectable implant to stimulate the sphenopalatine ganglion for treatment of acute ischaemic stroke up to 24 h from onset (ImpACT-24B): an international, randomised, double-blind, sham-controlled, pivotal trial

Author

Bornstein, Natan M, primary, Saver, Jeffrey L, additional, Diener, Hans Christoph, additional, Gorelick, Philip B, additional, Shuaib, Ashfaq, additional, Solberg, Yoram, additional, Thackeray, Lisa, additional, Savic, Milan, additional, Janelidze, Tamar, additional, Zarqua, Natia, additional, Yarnitsky, David, additional, Molina, Carlos A, additional, Hill, Michael, additional, Vaclavik, Daniel, additional, Skoloudik, David, additional, Fiksa, Jan, additional, Andersen, Grethe, additional, Jakala, Pekka, additional, Tatlisumak, Turgut, additional, Kuzmanovski, Igor, additional, Guillon, Benoit, additional, Chabriat, Hugues, additional, Mahagne, Marie Helene, additional, Timsit, Serge, additional, Ronziere, Thomas, additional, Ingorokva, Gocha, additional, Beridze, Maya, additional, Beridze, Mzia, additional, Kharaishvili, Nino, additional, Kakabadze, Nodar, additional, Griewing, Bernd, additional, Hobohm, Carsten, additional, Schneider, Dietmar, additional, Weimar, Christian, additional, Poppert, Holger, additional, Kimmig, Hubert, additional, Berrouschot, Joerg, additional, Ringleb, Peter, additional, Schwab, Stefan, additional, Kohrmann, Martin, additional, Kallmunzer, Bernd, additional, Kollmar, Rainer, additional, Endres, Matthias, additional, Hausler, Karl-Georg, additional, Cheung, Raymond, additional, Wai Hong Leung, Thomas, additional, Dorodnicov, Elena, additional, Halevi, Hen, additional, Auriel, Eitan, additional, Streifler, Jonathan, additional, Leker, Ronen, additional, Schwammenthal, Yvonne, additional, Toni, Danilo, additional, Agnelli, Giancarlo, additional, Caso, Valeria, additional, Słowik, Agnieszka, additional, Czlonkowska, Anna, additional, Lubinski, Ignacy, additional, Kochanowicz, Jan, additional, Sobolewski, Piotr, additional, Brola, Waldemar, additional, Salgado, Antonio Vasco, additional, Correia, Carlos, additional, Azevedo, Elsa, additional, Roriz, Jose, additional, Zarkov, Marija, additional, Petrovic, Zarko, additional, Krastev, Georgi, additional, Dvorak, Miloslav, additional, Rodriguez Campello, Ana, additional, Nunez, Antonio Gil, additional, Molina, Carlos, additional, Purroy, Francisco, additional, Marti-Fabregas, Joan, additional, Arenillas, Juan, additional, Alonso, Maria, additional, Cardona, Pedro, additional, Blanco Gonzalez, Miguel, additional, Tur, Silvia, additional, Segura Martin, Tomas, additional, Anzhelika, Payenok, additional, Shownkeen, Harish, additional, Concha, Mauricio, additional, Sethi, Pramod, additional, Sen, Souvik, additional, Zaidi, Syed, additional, and Devlin, Thomas, additional

Published
2019
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49. Cerebral microbleeds and stroke risk after ischaemic stroke or transient ischaemic attack: a pooled analysis of individual patient data from cohort studies

Author

Wilson, Duncan, primary, Ambler, Gareth, additional, Lee, Keon-Joo, additional, Lim, Jae-Sung, additional, Shiozawa, Masayuki, additional, Koga, Masatoshi, additional, Li, Linxin, additional, Lovelock, Caroline, additional, Chabriat, Hugues, additional, Hennerici, Michael, additional, Wong, Yuen Kwun, additional, Mak, Henry Ka Fung, additional, Prats-Sánchez, Luis, additional, Martínez-Domeño, Alejandro, additional, Inamura, Shigeru, additional, Yoshifuji, Kazuhisa, additional, Arsava, Ethem Murat, additional, Horstmann, Solveig, additional, Purrucker, Jan, additional, Lam, Bonnie Yin Ka, additional, Wong, Adrian, additional, Kim, Young Dae, additional, Song, Tae-Jin, additional, Schrooten, Maarten, additional, Lemmens, Robin, additional, Eppinger, Sebastian, additional, Gattringer, Thomas, additional, Uysal, Ender, additional, Tanriverdi, Zeynep, additional, Bornstein, Natan M, additional, Assayag, Einor Ben, additional, Hallevi, Hen, additional, Tanaka, Jun, additional, Hara, Hideo, additional, Coutts, Shelagh B, additional, Hert, Lisa, additional, Polymeris, Alexandros, additional, Seiffge, David J, additional, Lyrer, Philippe, additional, Algra, Ale, additional, Kappelle, Jaap, additional, Al-Shahi Salman, Rustam, additional, Jäger, Hans R, additional, Lip, Gregory Y H, additional, Mattle, Heinrich P, additional, Panos, Leonidas D, additional, Mas, Jean-Louis, additional, Legrand, Laurence, additional, Karayiannis, Christopher, additional, Phan, Thanh, additional, Gunkel, Sarah, additional, Christ, Nicolas, additional, Abrigo, Jill, additional, Leung, Thomas, additional, Chu, Winnie, additional, Chappell, Francesca, additional, Makin, Stephen, additional, Hayden, Derek, additional, Williams, David J, additional, Kooi, M Eline, additional, van Dam-Nolen, Dianne H K, additional, Barbato, Carmen, additional, Browning, Simone, additional, Wiegertjes, Kim, additional, Tuladhar, Anil M, additional, Maaijwee, Noortje, additional, Guevarra, Christine, additional, Yatawara, Chathuri, additional, Mendyk, Anne-Marie, additional, Delmaire, Christine, additional, Köhler, Sebastian, additional, van Oostenbrugge, Robert, additional, Zhou, Ying, additional, Xu, Chao, additional, Hilal, Saima, additional, Gyanwali, Bibek, additional, Chen, Christopher, additional, Lou, Min, additional, Staals, Julie, additional, Bordet, Régis, additional, Kandiah, Nagaendran, additional, de Leeuw, Frank-Erik, additional, Simister, Robert, additional, van der Lugt, Aad, additional, Kelly, Peter J, additional, Wardlaw, Joanna M, additional, Soo, Yannie, additional, Fluri, Felix, additional, Srikanth, Velandai, additional, Calvet, David, additional, Jung, Simon, additional, Kwa, Vincent I H, additional, Engelter, Stefan T, additional, Peters, Nils, additional, Smith, Eric E, additional, Yakushiji, Yusuke, additional, Orken, Dilek Necioglu, additional, Fazekas, Franz, additional, Thijs, Vincent, additional, Heo, Ji Hoe, additional, Mok, Vincent, additional, Veltkamp, Roland, additional, Ay, Hakan, additional, Imaizumi, Toshio, additional, Gomez-Anson, Beatriz, additional, Lau, Kui Kai, additional, Jouvent, Eric, additional, Rothwell, Peter M, additional, Toyoda, Kazunori, additional, Bae, Hee-Joon, additional, Marti-Fabregas, Joan, additional, Werring, David J, additional, Harkness, Kirsty, additional, Shaw, Louise, additional, Sword, Jane, additional, Mohd Nor, Azlisham, additional, Sharma, Pankaj, additional, Kelly, Deborah, additional, Harrington, Frances, additional, Randall, Marc, additional, Smith, Matthew, additional, Mahawish, Karim, additional, Elmarim, Abduelbaset, additional, Esisi, Bernard, additional, Cullen, Claire, additional, Nallasivam, Arumug, additional, Price, Christopher, additional, Barry, Adrian, additional, Roffe, Christine, additional, Coyle, John, additional, Hassan, Ahamad, additional, Birns, Jonathan, additional, Cohen, David, additional, Sekaran, Lakshmanan, additional, Parry-Jones, Adrian, additional, Parry, Anthea, additional, Hargroves, David, additional, Proschel, Harald, additional, Datta, Prabel, additional, Darawil, Khaled, additional, Manoj, Aravindakshan, additional, Burn, Mathew, additional, Patterson, Chris, additional, Giallombardo, Elio, additional, Smyth, Nigel, additional, Mansoor, Syed, additional, Anwar, Ijaz, additional, Marsh, Rachel, additional, Ispoglou, Sissi, additional, Chadha, Dinesh, additional, Prabhakaran, Mathuri, additional, Meenakishundaram, Sanjeevikumar, additional, O'Connell, Janice, additional, Scott, Jon, additional, Krishnamurthy, Vinodh, additional, Aghoram, Prasanna, additional, McCormick, Michael, additional, Sprigg, Nikola, additional, O'Mahony, Paul, additional, Cooper, Martin, additional, Choy, Lillian, additional, Wilkinson, Peter, additional, Leach, Simon, additional, Caine, Sarah, additional, Burger, Ilse, additional, Gunathilagan, Gunaratam, additional, Guyler, Paul, additional, Emsley, Hedley, additional, Davis, Michelle, additional, Manawadu, Dulka, additional, Pasco, Kath, additional, Mamun, Maam, additional, Luder, Robert, additional, Sajid, Mahmud, additional, Okwera, James, additional, Warburton, Elizabeth, additional, Saastamoinen, Kari, additional, England, Timothy, additional, Putterill, Janet, additional, Flossman, Enrico, additional, Power, Michael, additional, Dani, Krishna, additional, Mangion, David, additional, Suman, Appu, additional, Corrigan, John, additional, Lawrence, Enas, additional, Vahidassr, Djamil, additional, Shakeshaft, Clare, additional, Brown, Martin, additional, Charidimou, Andreas, additional, Cohen, Hannah, additional, Banerjee, Gargi, additional, Houlden, Henry, additional, White, Mark, additional, Yousry, Tarek, additional, Flossmann, Enrico, additional, Muir, Keith, additional, El-Koussy, Marwan, additional, Gratz, Pascal, additional, Molad, Jeremy, additional, Korczyn, Amos, additional, Kliper, Efrat, additional, Maeder, Philippe, additional, Gass, Achim, additional, Pachai, Chahin, additional, Bracoub, Luc, additional, Douste-Blazy, Marie-Yvonne, additional, Fratacci, Marie Dominique, additional, Vicaut, Eric, additional, Sato, Shoichiro, additional, Miwa, Kaori, additional, Fujita, Kyohei, additional, Ide, Toshihiro, additional, Ma, Henry, additional, Ly, John, additional, Singhal, Shahoo, additional, Chandra, Ronil, additional, Slater, Lee-Anne, additional, Soufan, Cathy, additional, Moran, Christopher, additional, Traenka, Christopher, additional, Thilemann, Sebastian, additional, Fladt, Joachim, additional, Gensicke, Henrik, additional, Bonati, Leo, additional, Kim, Beom Joon, additional, Han, Moon-Ku, additional, Kang, Jihoon, additional, Ko, Eunbin, additional, Yang, Mi Hwa, additional, Jang, Myung Suk, additional, Murphy, Sean, additional, Carty, Fiona, additional, Akijian, Layan, additional, Thornton, John, additional, Schembri, Mark, additional, Douven, Elles, additional, Delgado-Mederos;, Raquel, additional, Marín, Rebeca, additional, Camps-Renom, Pol, additional, Guisado-Alonso, Daniel, additional, Nuñez, Fidel, additional, Medrano-Martorell, Santiago, additional, Merino, Elisa, additional, Iida, Kotaro, additional, Ikeda, Syuhei, additional, Nishihara, Masashi, additional, Irie, Hiroyuki, additional, Demirelli, Derya Selcuk, additional, Medanta, Jayesh Modi, additional, Zerna, Charlotte, additional, Hernández, Maria Valdés, additional, Armitage, Paul, additional, Heye, Anna, additional, Muñoz-Maniega, Susana, additional, Sakka, Eleni, additional, Thrippleton, Michael, additional, Dennis, Martin, additional, Beigneux, Ysoline, additional, Silva, Mauro, additional, Venketasubramanian, Narayanaswamy, additional, Ho, Shu Leung, additional, Cheung, Raymond Tak Fai, additional, Chan, Koon Ho, additional, Teo, Kay Cheong, additional, Hui, Edward, additional, Kwan, Joseph Shiu Kwong, additional, Chang, Richard, additional, Tse, Man Yu, additional, Hoi, Chu Peng, additional, Chan, Chung Yan, additional, Chan, Oi Ling, additional, Cheung, Ryan Hoi Kit, additional, Wong, Edmund Ka Ming, additional, Leung, Kam Tat, additional, Tsang, Suk Fung, additional, Ip, Hing Lung, additional, Ma, Sze Ho, additional, Ma, Karen, additional, Fong, Wing Chi, additional, Li, Siu Hung, additional, Li, Richard, additional, Ng, Ping Wing, additional, Wong, Kwok Kui, additional, Liu, Wenyan, additional, Wong, Lawrence, additional, Ramos, Lino, additional, De Schryver, Els, additional, Jöbsis, Joost, additional, van der Sande, Jaap, additional, Brouwers, Paul, additional, Roos, Yvo, additional, Stam, Jan, additional, Bakker, Stef, additional, Verbiest, Henk, additional, Schoonewille, Wouter, additional, Linn, Cisca, additional, Hertzberger, Leopold, additional, van Gemert, Maarten, additional, Berntsen, Paul, additional, Hendrikse, Jeroen, additional, Nederkoorn, Paul, additional, Mess, Werner, additional, Koudstaal, Peter, additional, Leff, Alexander, additional, Ward, Nicholas, additional, Nachev, Parashkev, additional, Perry, Richard, additional, Ozkan, Hatice, additional, and Mitchell, John, additional

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2019
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