24 results on '"Cullell, Nàtalia"'
Search Results
2. A multitrait genetic study of hemostatic factors and hemorrhagic transformation after stroke treatment
- Author
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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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3. Causal role of lipid metabolome on the risk of ischemic stroke, its etiological subtypes, and long-term outcome: A Mendelian randomization study
- Author
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Martín-Campos, Jesús M., Cárcel-Márquez, Jara, Llucià-Carol, Laia, Lledós, Miquel, Cullell, Natàlia, Muiño, Elena, Gallego-Fabrega, Cristina, and Fernández-Cadenas, Israel
- Published
- 2023
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4. Multi‐phenotype analyses of hemostatic traits with cardiovascular events reveal novel genetic associations
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Temprano‐Sagrera, Gerard, Sitlani, Colleen M., Bone, William P., Martin‐Bornez, Miguel, Voight, Benjamin F., Morrison, Alanna C., Damrauer, Scott M., de Vries, Paul S., Smith, Nicholas L., Sabater‐Lleal, Maria, 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, Raffield, Laura M, Bielak, Lawrence F, Yanek, Lisa R, Kleber, Marcus E, Mueller, Martina, Kavousi, Maryam, Mangino, Massimo, Liu, Melissa, Brown, Michael R, Conomos, Matthew P, 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, Le, Ngoc‐Quynh, 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, Lindstrom, Sara, Wang, Lu, Smith, Erin N, Gordon, William, de Andrade, Mariza, Brody, Jennifer A, Pattee, Jack W, Haessler, Jeffrey, Brumpton, Ben M, Chasman, Daniel I, Suchon, Pierre, Turman, Constance, Germain, Marine, MacDonald, James, Braekkan, Sigrid K, Armasu, Sebastian M, Jackson, Rabecca D, Nielsen, Jonas B, Giulianini, Franco, Puurunen, Marja K, Ibrahim, Manal, Heckbert, Susan R, Bammler, Theo K, Frazer, Kelly A, McCauley, Bryan M, Taylor, Kent, Pankow, James S, Reiner, Alexander P, Gabrielsen, Maiken E, Deleuze, Jean‐François, O’Donnell, Chris J, Kim, Jihye, Kraft, Peter, Hansen, John‐Bjarne, Heit, John A, Kooperberg, Charles, Hveem, Kristian, Ridker, Paul M, Morange, Pierre‐Emmanuel, Johnson, Andrew D, Kabrhel, Christopher, Trégouët, David‐Alexandre, Malik, Rainer, Chauhan, Ganesh, Traylor, Matthew, Sargurupremraj, Muralidharan, Okada, Yukinori, Mishra, Aniket, Rutten‐Jacobs, Loes, Giese, Anne‐Katrin, van der Laan, Sander W, Gretarsdottir, Solveig, Anderson, Christopher D, Chong, Michael, Adams, Hieab HH, Ago, Tetsuro, Almgren, Peter, Amouyel, Philippe, Ay, Hakan, Bartz, Traci M, Benavente, Oscar R, Bevan, Steve, Boncoraglio, Giorgio B, Brown, Robert D, Butterworth, Adam S, Carrera, Caty, Carty, Cara L, Chen, Wei‐Min, Cole, John W, Correa, Adolfo, Cotlarciuc, Ioana, Cruchaga, Carlos, Danesh, John, de Bakker, Paul IW, DeStefano, Anita L, den Hoed, Marcel, Duan, Qing, Engelter, Stefan T, Falcone, Guido J, Gottesman, Rebecca F, Grewal, Raji P, Gudnason, Vilmundur, Gustafsson, Stefan, Harris, Tamara B, Hassan, Ahamad, Havulinna, Aki S, Holliday, Elizabeth G, Howard, George, Hsu, Fang‐Chi, Hyacinth, Hyacinth I, Arfan Ikram, M, Ingelsson, Erik, Irvin, Marguerite R, Jian, Xueqiu, Jiménez‐Conde, Jordi, Johnson, Julie A, Jukema, J Wouter, Kanai, Masahiro, Keene, Keith L, Kissela, Brett M, Kleindorfer, Dawn O, Kubo, Michiaki, Lange, Leslie A, Langefeld, Carl D, Langenberg, Claudia, Launer, Lenore J, Lee, Jin‐Moo, Lemmens, Robin, Leys, Didier, Lewis, Cathryn M, Lin, Wei‐Yu, Lindgren, Arne G, Lorentzen, Erik, Magnusson, Patrik K, Maguire, Jane, Manichaikul, Ani, McArdle, Patrick F, Meschia, James F, Mitchell, Braxton D, Mosley, Thomas H, Nalls, Michael A, Ninomiya, Toshiharu, O’Donnell, Martin J, Pulit, Sara L, Rannikmäe, Kristiina, Rexrode, Kathryn M, Rice, Kenneth, Rich, Stephen S, Rost, Natalia S, Rothwell, Peter M, Rundek, Tatjana, Sacco, Ralph L, Sakaue, Saori, Sale, Michele M, Salomaa, Veikko, Sapkota, Bishwa R, Schmidt, Reinhold, Schmidt, Carsten O, Schminke, Ulf, Sharma, Pankaj, Slowik, Agnieszka, Sudlow, Cathie LM, Tanislav, Christian, Tatlisumak, Turgut, Taylor, Kent D, Thijs, Vincent NS, Thorleifsson, Gudmar, Thorsteinsdottir, Unnur, Tiedt, Steffen, Tzourio, Christophe, van Duijn, Cornelia M, Walters, Matthew, Wareham, Nicholas J, Wassertheil‐Smoller, Sylvia, Wilson, James G, Yusuf, Salim, Amin, Najaf, Aparicio, Hugo S, Arnett, Donna K, Attia, John, Beiser, Alexa S, Berr, Claudine, Buring, Julie E, Bustamante, Mariana, Caso, Valeria, Cheng, Yu‐Ching, Hoan Choi, Seung, Chowhan, Ayesha, Cullell, Natalia, Dartigues, Jean‐François, Delavaran, Hossein, Delgado, Pilar, Dörr, Marcus, Engström, Gunnar, Ford, Ian, Gurpreet, Wander S, Hamsten, Anders, Heitsch, Laura, Hozawa, Atsushi, Ibanez, Laura, Ilinca, Andreea, Ingelsson, Martin, Iwasaki, Motoki, Jackson, Rebecca D, Jood, Katarina, Jousilahti, Pekka, Kaffashian, Sara, Kalra, Lalit, Kamouchi, Masahiro, Kitazono, Takanari, Kjartansson, Olafur, Kloss, Manja, Koudstaal, Peter J, Krupinski, Jerzy, Labovitz, Daniel L, Laurie, Cathy C, Levi, Christopher R, Li, Linxin, Lind, Lars, Lindgren, Cecilia M, Lioutas, Vasileios, Mei Liu, Yong, Lopez, Oscar L, Makoto, Hirata, Martinez‐Majander, Nicolas, Matsuda, Koichi, Minegishi, Naoko, Montaner, Joan, Morris, Andrew P, Muiño, Elena, Müller‐Nurasyid, Martina, Norrving, Bo, Ogishima, Soichi, Parati, Eugenio A, Reddy Peddareddygari, Leema, Pedersen, Nancy L, Pera, Joanna, Perola, Markus, Pezzini, Alessandro, Pileggi, Silvana, Rabionet, Raquel, Riba‐Llena, Iolanda, Ribasés, Marta, Romero, Jose R, Roquer, Jaume, Rudd, Anthony G, Sarin, Antti‐Pekka, Sarju, Ralhan, Sarnowski, Chloe, Sasaki, Makoto, Satizabal, Claudia L, Satoh, Mamoru, Sattar, Naveed, Sawada, Norie, Sibolt, Gerli, Sigurdsson, Ásgeir, Smith, Albert, Sobue, Kenji, Soriano‐Tárraga, Carolina, Stanne, Tara, Colin Stine, O, Stott, David J, Strauch, Konstantin, Takai, Takako, Tanaka, Hideo, Tanno, Kozo, Teumer, Alexander, Tomppo, Liisa, Torres‐Aguila, Nuria P, Touze, Emmanuel, Tsugane, Shoichiro, Uitterlinden, Andre G, Valdimarsson, Einar M, van der Lee, Sven J, Völzke, Henry, Wakai, Kenji, Weir, David, Williams, Stephen R, Wolfe, Charles DA, Wong, Quenna, Xu, Huichun, Yamaji, Taiki, Sanghera, Dharambir K, Melander, Olle, Jern, Christina, Strbian, Daniel, Fernandez‐Cadenas, Israel, Longstreth, W T, Rolfs, Arndt, Hata, Jun, Woo, Daniel, Rosand, Jonathan, Pare, Guillaume, Hopewell, Jemma C, Saleheen, Danish, Stefansson, Kari, Worrall, Bradford B, Kittner, Steven J, Seshadri, Sudha, Fornage, Myriam, Markus, Hugh S, Howson, Joanna MM, Kamatani, Yoichiro, Debette, Stephanie, and Dichgans, Martin
- Published
- 2022
- Full Text
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5. SARS-CoV-2 susceptibility and COVID-19 disease severity are associated with genetic variants affecting gene expression in a variety of tissues
- Author
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Neale, Benjamin M., Daly, Mark, Ganna, Andrea, Stevens, Christine, Pathak, Gita A., Andrews, Shea J., Kanai, Masahiro, Cordioli, Mattia, Karjalainen, Juha, Polimanti, Renato, Pirinen, Matti, Harerimana, Nadia, Veerapen, Kumar, Wolford, Brooke, Nguyen, Huy, Solomonson, Matthew, Liao, Rachel G., Chwialkowska, Karolina, Trankiem, Amy, Balaconis, Mary K., Hayward, Caroline, Richmond, Anne, Campbell, Archie, Morris, Marcela, Fawns-Ritchie, Chloe, Glessner, Joseph T., Shaw, Douglas M., Chang, Xiao, Polikowski, Hannah, Lauren, Petty E., Chen, Hung-Hsin, Wanying, Zhu, Hakonarson, Hakon, Porteous, David J., Below, Jennifer, North, Kari, McCormick, Joseph B., Timmers, Paul R.H.J., Wilson, James F., Tenesa, Albert, D’Mellow, Kenton, Kerr, Shona M., Niemi, Mari E.K., Nkambul, Lindokuhle, Aprile von Hohenstaufen, Kathrin, Sobh, Ali, Eltoukhy, Madonna M., Yassen, Amr M., Hegazy, Mohamed A.F., Okasha, Kamal, Eid, Mohammed A., Moahmed, Hanteera S., Shahin, Doaa, El-Sherbiny, Yasser M., Elhadidy, Tamer A., Abd Elghafar, Mohamed S., El-Jawhari, Jehan J., Mohamed, Attia A.S., Elnagdy, Marwa H., Samir, Amr, Abdel-Aziz, Mahmoud, Khafaga, Walid T., El-Lawaty, Walaa M., Torky, Mohamed S., El-shanshory, Mohamed R., Batini, Chiara, Lee, Paul H., Shrine, Nick, Williams, Alexander T., Tobin, Martin D., Guyatt, Anna L., John, Catherine, Packer, Richard J., Ali, Altaf, Free, Robert C., Wang, Xueyang, Wain, Louise V., Hollox, Edward J., Venn, Laura D., Bee, Catherine E., Adams, Emma L., Niavarani, Ahmadreza, Sharififard, Bahareh, Aliannejad, Rasoul, Amirsavadkouhi, Ali, Naderpour, Zeinab, Tadi, Hengameh Ansari, Aleagha, Afshar Etemadi, Ahmadi, Saeideh, Mohseni Moghaddam, Seyed Behrooz, Adamsara, Alireza, Saeedi, Morteza, Abdollahi, Hamed, Hosseini, Abdolmajid, Chariyavilaskul, Pajaree, Chamnanphon, Monpat, Suttichet, Thitima B., Shotelersuk, Vorasuk, Pongpanich, Monnat, Phokaew, Chureerat, Chetruengchai, Wanna, Jantarabenjakul, Watsamon, Putchareon, Opass, Torvorapanit, Pattama, Puthanakit, Thanyawee, Suchartlikitwong, Pintip, Hirankarn, Nattiya, Nilaratanakul, Voraphoj, Sodsai, Pimpayao, Brumpton, Ben M., Hveem, Kristian, Willer, Cristen, Zhou, Wei, Rogne, Tormod, Solligard, Erik, Åsvold, Bjørn Olav, Abedalthagafi, Malak, Alaamery, Manal, Alqahtani, Saleh, Baraka, Dona, Al Harthi, Fawz, Alsolm, Ebtehal, Safieh, Leen Abu, Alowayn, Albandary M., Alqubaishi, Fatimah, Al Mutairi, Amal, Mangul, Serghei, Alshareef, Abdulraheem, Sawaji, Mona, Almutairi, Mansour, Aljawini, Nora, Albesher, Nour, Arabi, Yaseen M., Mahmoud, Ebrahim S., Khattab, Amin K., Halawani, Roaa T., Alahmadey, Ziab Z., Albakri, Jehad K., Felemban, Walaa A., Suliman, Bandar A., Hasanato, Rana, Al-Awdah, Laila, Alghamdi, Jahad, AlZahrani, Deema, AlJohani, Sameera, Al-Afghani, Hani, Alrashed, May, AlDhawi, Nouf, AlBardis, Hadeel, Alkwai, Sarah, Alswailm, Moneera, Almalki, Faisal, Albeladi, Maha, Almohammed, Iman, Barhoush, Eman, Albader, Anoud, Massadeh, Salam, AlMalik, Abdulaziz, Alotaibi, Sara, Alghamdi, Bader, Jung, Junghyun, Fawzy, Mohammad S., Lee, Yunsung, Magnus, Per, Trogstad, Lill-Iren S., Helgeland, Øyvind, Harris, Jennifer R., Mangino, Massimo, Spector, Tim D., Emma, Duncan, Smieszek, Sandra P., Przychodzen, Bartlomiej P., Polymeropoulos, Christos, Polymeropoulos, Vasilios, Polymeropoulos, Mihael H., Fernandez-Cadenas, Israel, Perez-Tur, Jordi, Llucià-Carol, Laia, Cullell, Natalia, Muiño, Elena, Cárcel-Márquez, Jara, DeDiego, Marta L., Iglesias, Lara Lloret, Planas, Anna M., Soriano, Alex, Rico, Veronica, Agüero, Daiana, Bedini, Josep L., Lozano, Francisco, Domingo, Carlos, Robles, Veronica, Ruiz-Jaén, Francisca, Márquez, Leonardo, Gomez, Juan, Coto, Eliecer, Albaiceta, Guillermo M., García-Clemente, Marta, Dalmau, David, Arranz, Maria J., Dietl, Beatriz, Serra-Llovich, Alex, Soler, Pere, Colobrán, Roger, Martín-Nalda, Andrea, Martínez, Alba Parra, Bernardo, David, Rojo, Silvia, Fiz-López, Aida, Arribas, Elisa, Cal-Sabater, Paloma de la, Segura, Tomás, González-Villa, Esther, Serrano-Heras, Gemma, Martí-Fàbregas, Joan, Jiménez-Xarrié, Elena, de Felipe Mimbrera, Alicia, Masjuan, Jaime, García-Madrona, Sebastian, Domínguez-Mayoral, Anna, Villalonga, Joan Montaner, Menéndez-Valladares, Paloma, Chasman, Daniel I., Buring, Julie E., Ridker, Paul M., Franco, Giulianini, Sesso, Howard D., Manson, JoAnn E., Glessner, Joseph R., Medina-Gomez, Carolina, Uitterlinden, Andre G., Ikram, M. Arfan, Kristiansson, Kati, Koskelainen, Sami, Perola, Markus, Donner, Kati, Kivinen, Katja, Palotie, Aarno, Ripatti, Samuli, Ruotsalainen, Sanni, Kaunisto, Mari, FinnGen, Nakanishi, Tomoko, Butler-Laporte, Guillaume, Forgetta, Vincenzo, Morrison, David R., Ghosh, Biswarup, Laurent, Laetitia, Belisle, Alexandre, Henry, Danielle, Abdullah, Tala, Adeleye, Olumide, Mamlouk, Noor, Kimchi, Nofar, Afrasiabi, Zaman, Branka Vulesevic, Nardin Rezk, Bouab, Meriem, Guzman, Charlotte, Petitjean, Louis, Tselios, Chris, Xue, Xiaoqing, Schurr, Erwin, Afilalo, Jonathan, Afilalo, Marc, Oliveira, Maureen, Brenner, Bluma, Lepage, Pierre, Ragoussis, Jiannis, Auld, Daniel, Brassard, Nathalie, Durand, Madeleine, Chassé, Michaël, Kaufmann, Daniel E., Lathrop, G. Mark, Mooser, Vincent, Richards, J. Brent, Li, Rui, Adra, Darin, Rahmouni, Souad, Georges, Michel, Moutschen, Michel, Misset, Benoit, Darcis, Gilles, Guiot, Julien, Guntz, Julien, Azarzar, Samira, Gofflot, Stéphanie, Beguin, Yves, Claassen, Sabine, Malaise, Olivier, Huynen, Pascale, Meuris, Christelle, Thys, Marie, Jacques, Jessica, Léonard, Philippe, Frippiat, Frederic, Giot, Jean-Baptiste, Sauvage, Anne-Sophie, Von Frenckell, Christian, Belhaj, Yasmine, Lambermont, Bernard, Pigazzini, Sara, Nkambule, Lindokuhle, Daya, Michelle, Shortt, Jonathan, Rafaels, Nicholas, Wicks, Stephen J., Crooks, Kristy, Barnes, Kathleen C., Gignoux, Christopher R., Chavan, Sameer, Laisk, Triin, Läll, Kristi, Lepamets, Maarja, Mägi, Reedik, Esko, Tõnu, Reimann, Ene, Milani, Lili, Alavere, Helene, Metsalu, Kristjan, Puusepp, Mairo, Metspalu, Andres, Naaber, Paul, Laane, Edward, Pesukova, Jaana, Peterson, Pärt, Kisand, Kai, Tabri, Jekaterina, Allos, Raili, Hensen, Kati, Starkopf, Joel, Ringmets, Inge, Tamm, Anu, Kallaste, Anne, Bochud, Pierre-Yves, Rivolta, Carlo, Bibert, Stéphanie, Quinodoz, Mathieu, Kamdar, Dhryata, Boillat, Noémie, Nussle, Semira Gonseth, Albrich, Werner, Suh, Noémie, Neofytos, Dionysios, Erard, Véronique, Voide, Cathy, FHoGID, RegCOVID, P-PredictUs, SeroCOVID, CRiPSI, de Cid, Rafael, Galván-Femenía, Iván, Blay, Natalia, Carreras, Anna, Cortés, Beatriz, Farré, Xavier, Sumoy, Lauro, Moreno, Victor, Mercader, Josep Maria, Guindo-Martinez, Marta, Torrents, David, Kogevinas, Manolis, Garcia-Aymerich, Judith, Castaño-Vinyals, Gemma, Dobaño, Carlota, Renieri, Alessandra, Mari, Francesca, Fallerini, Chiara, Daga, Sergio, Benetti, Elisa, Baldassarri, Margherita, Fava, Francesca, Frullanti, Elisa, Valentino, Floriana, Doddato, Gabriella, Giliberti, Annarita, Tita, Rossella, Amitrano, Sara, Bruttini, Mirella, Croci, Susanna, Meloni, Ilaria, Mencarelli, Maria Antonietta, Lo Rizzo, Caterina, Pinto, Anna Maria, Beligni, Giada, Tommasi, Andrea, Di Sarno, Laura, Palmieri, Maria, Carriero, Miriam Lucia, Alaverdian, Diana, Busani, Stefano, Bruno, Raffaele, Vecchia, Marco, Belli, Mary Ann, Picchiotti, Nicola, Sanarico, Maurizio, Gori, Marco, Furini, Simone, Mantovani, Stefania, Ludovisi, Serena, Mondelli, Mario Umberto, Castelli, Francesco, Quiros-Roldan, Eugenia, Antoni, Melania Degli, Zanella, Isabella, Vaghi, Massimo, Rusconi, Stefano, Siano, Matteo, Montagnani, Francesca, Emiliozzi, Arianna, Fabbiani, Massimiliano, Rossetti, Barbara, Bargagli, Elena, Bergantini, Laura, D’Alessandro, Miriana, Cameli, Paolo, Bennett, David, Anedda, Federico, Marcantonio, Simona, Scolletta, Sabino, Franchi, Federico, Mazzei, Maria Antonietta, Guerrini, Susanna, Conticini, Edoardo, Cantarini, Luca, Frediani, Bruno, Tacconi, Danilo, Spertilli, Chiara, Feri, Marco, Donati, Alice, Scala, Raffaele, Guidelli, Luca, Spargi, Genni, Corridi, Marta, Nencioni, Cesira, Croci, Leonardo, Bandini, Maria, Caldarelli, Gian Piero, Piacentini, Paolo, Desanctis, Elena, Cappelli, Silvia, Canaccini, Anna, Verzuri, Agnese, Anemoli, Valentina, Ognibene, Agostino, Pancrazzi, Alessandro, Lorubbio, Maria, D’Arminio Monforte, Antonella, Miraglia, Federica Gaia, Girardis, Massimo, Venturelli, Sophie, Cossarizza, Andrea, Antinori, Andrea, Vergori, Alessandra, Gabrieli, Arianna, Riva, Agostino, Francisci, Daniela, Schiaroli, Elisabetta, Paciosi, Francesco, Scotton, Pier Giorgio, Andretta, Francesca, Panese, Sandro, Scaggiante, Renzo, Gatti, Francesca, Parisi, Saverio Giuseppe, Baratti, Stefano, Della Monica, Matteo, Piscopo, Carmelo, Capasso, Mario, Russo, Roberta, Andolfo, Immacolata, Iolascon, Achille, Fiorentino, Giuseppe, Carella, Massimo, Castori, Marco, Merla, Giuseppe, Squeo, Gabriella Maria, Aucella, Filippo, Raggi, Pamela, Marciano, Carmen, Perna, Rita, Bassetti, Matteo, Di Biagio, Antonio, Sanguinetti, Maurizio, Masucci, Luca, Valente, Serafina, Mandalà, Marco, Giorli, Alessia, Salerni, Lorenzo, Zucchi, Patrizia, Parravicini, Pierpaolo, Menatti, Elisabetta, Trotta, Tullio, Giannattasio, Ferdinando, Coiro, Gabriella, Lena, Fabio, Coviello, Domenico A., Mussini, Cristina, Martinelli, Enrico, Mancarella, Sandro, Tavecchia, Luisa, Crotti, Lia, Gabbi, Chiara, Rizzi, Marco, Maggiolo, Franco, Ripamonti, Diego, Bachetti, Tiziana, La Rovere, Maria Teresa, Sarzi-Braga, Simona, Bussotti, Maurizio, Ceri, Stefano, Pinoli, Pietro, Raimondi, Francesco, Biscarini, Filippo, Stella, Alessandra, Zguro, Kristina, Capitani, Katia, Suardi, Claudia, Dei, Simona, Parati, Gianfranco, Ravaglia, Sabrina, Artuso, Rosangela, Bottà, Giordano, Di Domenico, Paolo, Rancan, Ilaria, Francesco Bianchi, Antonio Perrella, Romani, Davide, Bergomi, Paola, Catena, Emanuele, Colombo, Riccardo, Tanfoni, Marco, Vincenti, Antonella, Ferri, Claudio, Grassi, Davide, Pessina, Gloria, Tumbarello, Mario, Di Pietro, Massimo, Sabrina, Ravaglia, Luchi, Sauro, Barbieri, Chiara, Acquilini, Donatella, Andreucci, Elena, Segala, Francesco Vladimiro, Tiseo, Giusy, Falcone, Marco, Lista, Mirjam, Poscente, Monica, De Vivo, Oreste, Petrocelli, Paola, Guarnaccia, Alessandra, Baroni, Silvia, Smith, Albert V., Boughton, Andrew P., Li, Kevin W., LeFaive, Jonathon, Annis, Aubrey, Justice, Anne E., Mirshahi, Tooraj, Chittoor, Geetha, Josyula, Navya Shilpa, Kosmicki, Jack A., Ferreira, Manuel A.R., Leader, Joseph B., Carey, Dave J., Gass, Matthew C., Horowitz, Julie E., Cantor, Michael N., Yadav, Ashish, Baras, Aris, Abecasis, Goncalo R., van Heel, David A., Hunt, Karen A., Mason, Dan, Huang, Qin Qin, Finer, Sarah, Genes & Health Research Team, Trivedi, Bhavi, Griffiths, Christopher J., Martin, Hilary C., Wright, John, Trembath, Richard C., Soranzo, Nicole, Zhao, Jing Hua, Butterworth, Adam S., Danesh, John, Di Angelantonio, Emanuele, Marike Boezen, Lude Franke, Deelen, Patrick, Claringbould, Annique, Lopera, Esteban, Warmerdam, Robert, Vonk, Judith.M., van Blokland, Irene, Lanting, Pauline, Ori, Anil P.S., Sebastian Zöllner, Brooke Wolford, Wang, Jiongming, Beck, Andrew, Peloso, Gina, Ho, Yuk-Lam, Sun, Yan V., Huffman, Jennifer E., O’Donnell, Christopher J., Cho, Kelly, Tsao, Phil, Gaziano, J. Michael, Nivard, Michel (M.G.), de geus, Eco (E.J.C.), Bartels, Meike, Hottenga, Jouke Jan, Weiss, Scott T., Karlson, Elizabeth W., Smoller, Jordan W., Green, Robert C., Anne Feng, Yen-Chen, Mercader, Josep, Murphy, Shawn N., Meigs, James B., Woolley, Ann E., Perez, Emma F., Rader, Daniel, Verma, Anurag, Ritchie, Marylyn D., Li, Binglan, Verma, Shefali S., Lucas, Anastasia, Bradford, Yuki, Zeberg, Hugo, Frithiof, Robert, Hultström, Michael, Lipcsey, Miklos, Nkambul, Lindo, Tardif, Nicolas, Rooyackers, Olav, Grip, Jonathan, Maricic, Tomislav, Karczewski, Konrad J., Atkinson, Elizabeth G., Tsuo, Kristin, Baya, Nikolas, Turley, Patrick, Gupta, Rahul, Callier, Shawneequa, Walters, Raymond K., Palmer, Duncan S., Sarma, Gopal, Cheng, Nathan, Lu, Wenhan, Bryant, Sam, Churchhouse, Claire, Cusick, Caroline, Goldstein, Jacqueline I., King, Daniel, Seed, Cotton, Finucane, Hilary, Martin, Alicia R., Satterstrom, F. Kyle, Wilson, Daniel J., Armstrong, Jacob, Rudkin, Justine K., Band, Gavin, Earle, Sarah G., Lin, Shang-Kuan, Arning, Nicolas, Crook, Derrick W., Wyllie, David H., O’Connell, Anne Marie, Spencer, Chris C.A., Koelling, Nils, Caulfield, Mark J., Scott, Richard H., Fowler, Tom, Moutsianas, Loukas, Kousathanas, Athanasios, Pasko, Dorota, Walker, Susan, Rendon, Augusto, Stuckey, Alex, Odhams, Christopher A., Rhodes, Daniel, Chan, Georgia, Arumugam, Prabhu, Ball, Catherine A., Hong, Eurie L., Rand, Kristin, Girshick, Ahna, Guturu, Harendra, Baltzell, Asher Haug, Roberts, Genevieve, Park, Danny, Coignet, Marie, McCurdy, Shannon, Knight, Spencer, Partha, Raghavendran, Rhead, Brooke, Zhang, Miao, Berkowitz, Nathan, Gaddis, Michael, Noto, Keith, Ruiz, Luong, Pavlovic, Milos, Sloofman, Laura G., Charney, Alexander W., Beckmann, Noam D., Schadt, Eric E., Jordan, Daniel M., Thompson, Ryan C., Gettler, Kyle, Abul-Husn, Noura S., Ascolillo, Steven, Buxbaum, Joseph D., Chaudhary, Kumardeep, Cho, Judy H., Itan, Yuval, Kenny, Eimear E., Belbin, Gillian M., Sealfon, Stuart C., Sebra, Robert P., Salib, Irene, Collins, Brett L., Levy, Tess, Britvan, Bari, Keller, Katherine, Tang, Lara, Peruggia, Michael, Hiester, Liam L., Niblo, Kristi, Aksentijevich, Alexandra, Labkowsky, Alexander, Karp, Avromie, Zlatopolsky, Menachem, Preuss, Michael, Loos, Ruth J.F., Nadkarni, Girish N., Do, Ron, Hoggart, Clive, Choi, Sam, Underwood, Slayton J., O’Reilly, Paul, Huckins, Laura M., Zyndorf, Marissa, D’Antonio, Matteo, Nguyen, Jennifer P., Arthur, Timothy D., Matsui, Hiroko, D’Antonio-Chronowska, Agnieszka, and Frazer, Kelly A.
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- 2021
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6. DNA Methylation in Stroke. Update of Latest Advances
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Krupinski, Jerzy, Carrera, Caty, Muiño, Elena, Torres, Nuria, Al-Baradie, Raid, Cullell, Natalia, and Fernandez-Cadenas, Israel
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- 2018
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7. Sleep/wake cycle alterations as a cause of neurodegenerative diseases: A Mendelian randomization study
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Cullell, Natalia, Cárcel-Márquez, Jara, Gallego-Fábrega, Cristina, Muiño, Elena, Llucià-Carol, Laia, Lledós, Miquel, Amaut, Karol Enrique Uscamaita, Krupinski, Jerzy, and Fernández-Cadenas, Israel
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- 2021
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8. Genetic Architecture of Ischaemic Strokes after COVID-19 Shows Similarities with Large Vessel Strokes
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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.
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- 2023
9. Table_2_A Polygenic Risk Score Based on a Cardioembolic Stroke Multitrait Analysis Improves a Clinical Prediction Model for This Stroke Subtype.XLSX
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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.
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- 2022
10. Additional file 1 of Altered methylation pattern in EXOC4 is associated with stroke outcome: an epigenome-wide association study
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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
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- 2022
11. Supplementary Material DNA methylation is associated with ischemic stroke risk: An Epigenome-Wide association study
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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
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- 2022
12. Supplemental Material Biological age acceleration is lower in women with Ischemic Stroke compared to men
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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
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- 2022
13. A Polygenic Risk Score Based on a Cardioembolic Stroke Multitrait Analysis Improves a Clinical Prediction Model for This Stroke Subtype
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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.
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- 2022
14. Biological Age Acceleration Is Lower in Women with Ischemic Stroke Compared to Men
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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
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- 2022
15. Genome-Wide Studies in Ischaemic Stroke: Are Genetics Only Useful for Finding Genes?
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Instituto de Salud Carlos III, Red de Enfermedades Vasculares Cerebrales (España), Fundació La Marató de TV3, European Commission, Generalitat de Catalunya, Gallego-Fabrega, Cristina, Muiño, Elena, Cárcel-Márquez, Jara, Llucià-Carol, Laia, Lledós, Miquel, Martín-Campos, Jesús M., Cullell, Nàtalia, Fernández-Cadenas, Israel, Instituto de Salud Carlos III, Red de Enfermedades Vasculares Cerebrales (España), Fundació La Marató de TV3, European Commission, Generalitat de Catalunya, Gallego-Fabrega, Cristina, Muiño, Elena, Cárcel-Márquez, Jara, Llucià-Carol, Laia, Lledós, Miquel, Martín-Campos, Jesús M., Cullell, Nàtalia, and Fernández-Cadenas, Israel
- Abstract
Ischaemic stroke is a complex disease with some degree of heritability. This means that heritability factors, such as genetics, could be risk factors for ischaemic stroke. The era of genome-wide studies has revealed some of these heritable risk factors, although the data generated by these studies may also be useful in other disciplines. Analysis of these data can be used to understand the biological mechanisms associated with stroke risk and stroke outcome, to determine the causality between stroke and other diseases without the need for expensive clinical trials, or to find potential drug targets with higher success rates than other strategies. In this review we will discuss several of the most relevant studies regarding the genetics of ischaemic stroke and the potential use of the data generated.
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- 2022
16. DNA Methylation and Ischemic Stroke Risk: An Epigenome-Wide Association Study
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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.
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- 2022
17. Genome-wide transcriptome study in skin biopsies reveals an association of E2F4 with cadasil and cognitive impairment
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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
18. Pharmacogenetics studies in stroke patients treated with rtPA: A review of the most interesting findings
- Author
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Llucià-Carol, Laia, Muiño, Elena, Gallego-Fabrega, Cristina, Cárcel-Márquez, Jara, Martín-Campos, Jesús M., Lledós, Miquel, Cullell, Nàtalia, Fernández-Cadenas, Israel, Llucià-Carol, Laia, Muiño, Elena, Gallego-Fabrega, Cristina, Cárcel-Márquez, Jara, Martín-Campos, Jesús M., Lledós, Miquel, Cullell, Nàtalia, and Fernández-Cadenas, Israel
- Abstract
Recombinant tissue-plasminogen activator (rtPA) is the only drug used during the acute phase of stroke. Despite its important benefits, a percentage of patients suffer symptomatic hemorrhagic transformations or a lack of early recanalization rates. These undesirable effects are associated with acute neurological and long-term functional deterioration. For the past 20 years, pharmacogenetic studies have tried to find the genetic risk factors associated with rtPA response. Most of these studies have used a gene-candidate strategy; however, recent genome-wide association studies have emerged indicating that genetic predisposition could modulate rtPA response. This review summarizes the most interesting findings in this field, including which genes and genetic variations are associated with hemorrhagic transformations and recanalization rates after thrombolytic therapy.
- Published
- 2021
19. A parsimonious score with a free web tool for predicting disability after an ischemic stroke: the Parsifal Score
- Author
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Instituto de Salud Carlos III, Fundació La Marató de TV3, European Commission, Agència de Gestió d'Ajuts Universitaris i de Recerca, Muiño, Elena, Bustamante, Alejandro, Rodríguez-Campello, Ana, Gallego-Fabrega, Cristina, Ois, Ángel, Carrera, Caty, Cullell, Nàtalia, Torres-Águila, Nuria P., Cárcel-Márquez, Jara, Rubiera, M., Molina, Carlos A., Cuadrado-Godia, Elisa, Giralt-Steinhauer, Eva, Jiménez-Conde, Jordi, Montaner, Joan, Fernández-Cadenas, Israel, Roquer, Jaume, Instituto de Salud Carlos III, Fundació La Marató de TV3, European Commission, Agència de Gestió d'Ajuts Universitaris i de Recerca, Muiño, Elena, Bustamante, Alejandro, Rodríguez-Campello, Ana, Gallego-Fabrega, Cristina, Ois, Ángel, Carrera, Caty, Cullell, Nàtalia, Torres-Águila, Nuria P., Cárcel-Márquez, Jara, Rubiera, M., Molina, Carlos A., Cuadrado-Godia, Elisa, Giralt-Steinhauer, Eva, Jiménez-Conde, Jordi, Montaner, Joan, Fernández-Cadenas, Israel, and Roquer, Jaume
- Abstract
[Background] Most of the models to predict prognosis after an ischemic stroke include complex mathematical equations or too many variables, making them difficult to use in the daily clinic. We want to predict disability 3 months after an ischemic stroke in an independent patient not receiving recanalization treatment within the first 24 h, using a minimum set of variables and an easy tool to facilitate its implementation. As a secondary aim, we calculated the capacity of the score to predict an excellent/devastating outcome and mortality., [Methods] Eight hundred and forty-four patients were evaluated. A multivariable ordinal logistic regression was used to obtain the score. The Modified Rankin Scale (mRS) was used to estimate disability at the third month. The results were replicated in another independent cohort (378 patients). The “polr” function of R was used to perform the regression, stratifying the sample into seven groups with different cutoffs (from mRS 0 to 6)., [Results] The Parsifal score was generated with: age, previous mRS, initial NIHSS, glycemia on admission, and dyslipidemia. This score predicts disability with an accuracy of 80–76% (discovery–replication cohorts). It has an AUC of 0.86 in the discovery and replication cohort. The specificity was 90–80% (discovery–replication cohorts); while, the sensitivity was 64–74% (discovery–replication cohorts). The prediction of an excellent or devastating outcome, as well as mortality, obtained good discrimination with AUC > 0.80., [Conclusions] The Parsifal Score is a model that predicts disability at the third month, with only five variables, with good discrimination and calibration, and being replicated in an independent cohort.
- Published
- 2020
20. Genome-Wide Association Study of VKORC1 and CYP2C9 on acenocoumarol dose, stroke recurrence and intracranial haemorrhage in Spain
- Author
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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
21. A Genome-Wide Meta-Analysis
- Author
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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
22. A Genome-Wide Meta-Analysis
- Author
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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
23. Clinical Variables and Genetic Risk Factors Associated with the Acute Outcome of Ischemic Stroke: A Systematic Review
- Author
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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
24. Genome-Wide Association Study of White Blood Cell Counts in Patients With Ischemic Stroke
- Author
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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
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