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1. DNA methylation and stroke prognosis: an epigenome-wide association study

Author: Jiménez-Balado, Joan, Fernández-Pérez, Isabel, Gallego-Fábrega, Cristina, Lazcano, Uxue, Soriano-Tárraga, Carolina, Vallverdú-Prats, Marta, Mola-Caminal, Marina, Rey-Álvarez, Lucía, Macias-Gómez, Adrià, Suárez-Pérez, Antoni, Giralt-Steinhauer, Eva, Rodríguez-Campello, Ana, Cuadrado-Godia, Elisa, Ois, Ángel, Esteller, Manel, Roquer, Jaume, Fernández-Cadenas, Israel, and Jiménez-Conde, Jordi
Published: 2024
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2. Role of PATJ in stroke prognosis by modulating endothelial to mesenchymal transition through the Hippo/Notch/PI3K axis

Author: Medina-Dols, Aina, Cañellas, Guillem, Capó, Toni, Solé, Montse, Mola-Caminal, Marina, Cullell, Natalia, Jaume, Marina, Nadal-Salas, Laura, Llinàs, Jaume, Gómez, Lluis, Tur, Silvia, Jiménez, Carmen, Díaz, Rosa M., Carrera, Caty, Muiño, Elena, Gallego-Fabrega, Cristina, Soriano-Tárraga, Carolina, Ruiz-Guerra, Laura, Pol-Fuster, Josep, Asensio, Víctor, Muncunill, Josep, Fleischer, Aarne, Iglesias, Amanda, Giralt-Steinhauer, Eva, Lazcano, Uxue, Fernández-Pérez, Isabel, Jiménez-Balado, Joan, Gabriel-Salazar, Marina, Garcia-Gabilondo, Miguel, Lei, Ting, Torres-Aguila, Nuria-Paz, Cárcel-Márquez, Jara, Lladó, Jerònia, Olmos, Gabriel, Rosell, Anna, Montaner, Joan, Planas, Anna M., Rabionet, Raquel, Hernández-Guillamon, Mar, Jiménez-Conde, Jordi, Fernández-Cadenas, Israel, and Vives-Bauzá, Cristòfol
Published: 2024
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3. 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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4. Causal role of lipid metabolome on the risk of ischemic stroke, its etiological subtypes, and long-term outcome: A Mendelian randomization study

Author: 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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5. Stroke genetics informs drug discovery and risk prediction across ancestries

Author: Mishra, Aniket, Malik, Rainer, Hachiya, Tsuyoshi, Jürgenson, 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, Cárcel-Márquez, 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, Børte, 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, Børge 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., Trégouët, David-Alexandre, Trompet, Stella, Tuladhar, Anil Man, Tybjærg-Hansen, Anne, van Vugt, Marion, Vibo, Riina, Verma, Shefali S., Wiggins, Kerri L., Wennberg, Patrik, Woo, Daniel, Wilson, Peter W. F., Xu, Huichun, Yang, Qiong, Yoon, Kyungheon, 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 M. M., Irvin, Marguerite R., Adams, Hieab, Wassertheil-Smoller, Sylvia, Christensen, Kaare, Ikram, Mohammad A., Rundek, Tatjana, Worrall, Bradford B., Lathrop, G. Mark, Riaz, Moeen, Simonsick, Eleanor M., Kõrv, Janika, França, Paulo H. C., Zand, Ramin, Prasad, Kameshwar, Frikke-Schmidt, Ruth, de Leeuw, Frank-Erik, Liman, Thomas, Haeusler, Karl Georg, Ruigrok, Ynte M., Heuschmann, Peter Ulrich, Longstreth, W. T., Jung, Keum Ji, Bastarache, Lisa, Paré, Guillaume, Damrauer, Scott M., Chasman, Daniel I., Rotter, Jerome I., Anderson, Christopher D., Zwart, John-Anker, Niiranen, Teemu J., Fornage, Myriam, Liaw, Yung-Po, Seshadri, Sudha, Fernández-Cadenas, Israel, Walters, Robin G., Ruff, Christian T., Owolabi, Mayowa O., Huffman, Jennifer E., Milani, Lili, Kamatani, Yoichiro, Dichgans, Martin, and Debette, Stephanie
Published: 2022
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6. Multi‐phenotype analyses of hemostatic traits with cardiovascular events reveal novel genetic associations

Author: 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
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7. Altered methylation pattern in EXOC4 is associated with stroke outcome: an epigenome-wide association study

Author: Cullell, Natalia, Soriano-Tárraga, Carolina, Gallego-Fábrega, Cristina, Cárcel-Márquez, Jara, Muiño, Elena, Llucià-Carol, Laia, Lledós, Miquel, Esteller, Manel, de Moura, Manuel Castro, Montaner, Joan, Rosell, Anna, Delgado, Pilar, Martí-Fábregas, Joan, Krupinski, Jerzy, Roquer, Jaume, Jiménez-Conde, Jordi, and Fernández-Cadenas, Israel
Published: 2022
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8. Genetic basis of lacunar stroke: a pooled analysis of individual patient data and genome-wide association studies

Author: Traylor, Matthew, Persyn, Elodie, Tomppo, Liisa, Klasson, Sofia, Abedi, Vida, Bakker, Mark K, Torres, Nuria, Li, Linxin, Bell, Steven, Rutten-Jacobs, Loes, Tozer, Daniel J, Griessenauer, Christoph J, Zhang, Yanfei, Pedersen, Annie, Sharma, Pankaj, Jimenez-Conde, Jordi, Rundek, Tatjana, Grewal, Raji P, Lindgren, Arne, Meschia, James F, Salomaa, Veikko, Havulinna, Aki, Kourkoulis, Christina, Crawford, Katherine, Marini, Sandro, Mitchell, Braxton D, Kittner, Steven J, Rosand, Jonathan, Dichgans, Martin, Jern, Christina, Strbian, Daniel, Fernandez-Cadenas, Israel, Zand, Ramin, Ruigrok, Ynte, Rost, Natalia, Lemmens, Robin, Rothwell, Peter M, Anderson, Christopher D, Wardlaw, Joanna, Lewis, Cathryn M, and Markus, Hugh S
Published: 2021
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9. Epigenome-wide association study of COVID-19 severity with respiratory failure

Author: Castro de Moura, Manuel, Davalos, Veronica, Planas-Serra, Laura, Alvarez-Errico, Damiana, Arribas, Carles, Ruiz, Montserrat, Aguilera-Albesa, Sergio, Troya, Jesús, Valencia-Ramos, Juan, Vélez-Santamaria, Valentina, Rodríguez-Palmero, Agustí, Villar-Garcia, Judit, Horcajada, Juan P., Albu, Sergiu, Casasnovas, Carlos, Rull, Anna, Reverte, Laia, Dietl, Beatriz, Dalmau, David, Arranz, Maria J., Llucià-Carol, Laia, Planas, Anna M., Pérez-Tur, Jordi, Fernandez-Cadenas, Israel, Villares, Paula, Tenorio, Jair, Colobran, Roger, Martin-Nalda, Andrea, Soler-Palacin, Pere, Vidal, Francesc, Pujol, Aurora, and Esteller, Manel
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. Publisher Correction: Stroke genetics informs drug discovery and risk prediction across ancestries

Author: Mishra, Aniket, Malik, Rainer, Hachiya, Tsuyoshi, Jürgenson, 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, Cárcel-Márquez, 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, Børte, 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, Børge 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., Trégouët, David-Alexandre, Trompet, Stella, Tuladhar, Anil Man, Tybjærg-Hansen, Anne, van Vugt, Marion, Vibo, Riina, Verma, Shefali S., Wiggins, Kerri L., Wennberg, Patrik, Woo, Daniel, Wilson, Peter W. F., Xu, Huichun, Yang, Qiong, Yoon, Kyungheon, 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 M. M., Irvin, Marguerite R., Adams, Hieab, Wassertheil-Smoller, Sylvia, Christensen, Kaare, Ikram, Mohammad A., Rundek, Tatjana, Worrall, Bradford B., Lathrop, G. Mark, Riaz, Moeen, Simonsick, Eleanor M., Kõrv, Janika, França, Paulo H. C., Zand, Ramin, Prasad, Kameshwar, Frikke-Schmidt, Ruth, de Leeuw, Frank-Erik, Liman, Thomas, Haeusler, Karl Georg, Ruigrok, Ynte M., Heuschmann, Peter Ulrich, Longstreth, W. T., Jung, Keum Ji, Bastarache, Lisa, Paré, Guillaume, Damrauer, Scott M., Chasman, Daniel I., Rotter, Jerome I., Anderson, Christopher D., Zwart, John-Anker, Niiranen, Teemu J., Fornage, Myriam, Liaw, Yung-Po, Seshadri, Sudha, Fernández-Cadenas, Israel, Walters, Robin G., Ruff, Christian T., Owolabi, Mayowa O., Huffman, Jennifer E., Milani, Lili, Kamatani, Yoichiro, Dichgans, Martin, and Debette, Stephanie
Published: 2022
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12. Genome-wide transcriptome study in skin biopsies reveals an association of E2F4 with cadasil and cognitive impairment

Author: Muiño, Elena, Maisterra, Olga, Jiménez-Balado, Joan, Cullell, Natalia, Carrera, Caty, Torres-Aguila, Nuria P., Cárcel-Márquez, Jara, Gallego-Fabrega, Cristina, Lledós, Miquel, González-Sánchez, Jonathan, Olmos-Alpiste, Ferran, Espejo, Eva, March, Álvaro, Pujol, Ramón, Rodríguez-Campello, Ana, Romeral, Gemma, Krupinski, Jurek, Martí-Fàbregas, Joan, Montaner, Joan, Roquer, Jaume, and Fernández-Cadenas, Israel
Published: 2021
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13. Cardioembolic Ischemic Stroke Gene Expression Fingerprint in Blood: a Systematic Review and Verification Analysis

Author: García-Berrocoso, Teresa, Palà, Elena, Consegal, Marta, Piccardi, Benedetta, Negro, Alex, Gill, Natalia, Penalba, Anna, Huerga Encabo, Hector, Fernández-Cadenas, Israel, Meisel, Andreas, Meisel, Christian, Jickling, Glen C., Muñoz, Miguel Ángel, Clúa-Espuny, Josep Lluis, Pedrote, Alonso, Pagola, Jorge, Juega, Jesús, Bustamante, Alejandro, and Montaner, Joan
Published: 2020
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14. Systematic Review of Cysteine-Sparing NOTCH3 Missense Mutations in Patients with Clinical Suspicion of CADASIL

Author: Muiño, Elena, primary, Gallego-Fabrega, Cristina, primary, Cullell, Natalia, primary, Carrera, Caty, primary, Torres, Nuria, primary, Krupinski, Jurek, primary, Roquer, Jaume, primary, Montaner, Joan, primary, and Fernández-Cadenas, Israel, primary
Published: 2020
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15. Genetic Architecture of Ischaemic Strokes after COVID-19 Shows Similarities with Large Vessel Strokes

Author: Llucià-Carol, Laia, primary, Muiño, Elena, additional, Cullell, Natalia, additional, Cárcel-Márquez, Jara, additional, Lledós, Miquel, additional, Gallego-Fabrega, Cristina, additional, Martin-Campos, Jesús, additional, Martí-Fàbregas, Joan, additional, Aguilera-Simón, Ana, additional, Planas, Anna M., additional, DeDiego, Marta L., additional, de Felipe Mimbrera, Alicia, additional, Masjuan, Jaime, additional, García-Madrona, Sebastián, additional, Segura, Tomás, additional, González-Villar, Esther, additional, Serrano-Heras, Gemma, additional, Domínguez Mayoral, Ana, additional, Menéndez-Valladares, Paloma, additional, Montaner, Joan, additional, Migeotte, Isabelle, additional, Rahmouni, Souad, additional, Darcis, Gilles, additional, Bernardo, David, additional, Rojo, Silvia, additional, Schulte, Eva C., additional, Protzer, Ulrike, additional, Fricke, Lisa, additional, Winter, Christof, additional, Niemi, Mari E. K., additional, Cordioli, Mattia, additional, Delgado, Pilar, additional, and Fernández-Cadenas, Israel, additional
Published: 2023
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16. Host factor PLAC8 is required for pancreas infection by SARS-CoV-2

Author: Ibargüen-González, Lesly, primary, Heller, Sandra, additional, DeDiego, Marta L., additional, García, Darío López-, additional, Gómez-Valero, Alba M, additional, Barth, Thomas FE, additional, Gallego, Patricia, additional, Fernández-Cadenas, Israel, additional, Alzate-Piñol, Sayoa, additional, Crespí, Catalina, additional, Mena-Guerrero, Julieth A, additional, Cisneros-Barroso, Eugenia, additional, Ugalde, Alejandro P., additional, Bretones, Gabriel, additional, Steenblock, Charlotte, additional, Kleger, Alexander, additional, and Barceló, Carles, additional
Published: 2023
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17. Ischaemic stroke patients present sex differences in gut microbiota

Author: Lledós, Miquel, primary, Prats‐Sánchez, Luís, additional, Llucià‐Carol, Laia, additional, Cárcel‐Márquez, Jara, additional, Muiño, Elena, additional, Cullell, Natalia, additional, Gallego‐Fabrega, Cristina, additional, Martín‐Campos, Jesús M., additional, Aguilera‐Simón, Ana, additional, Guasch‐Jiménez, Marina, additional, Guisado‐Alonso, Daniel, additional, Ramos‐Pachón, Anna, additional, Martínez‐Domeño, Alejandro, additional, Izquierdo, Artur, additional, Marín, Rebeca, additional, Camps‐Renom, Pol, additional, Martí‐Fàbregas, Joan, additional, and Fernández‐Cadenas, Israel, additional
Published: 2023
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18. Sleep/wake cycle alterations as a cause of neurodegenerative diseases: A Mendelian randomization study

Author: 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
Published: 2021
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19. Generation and Applicability of Genetic Risk Scores (GRS) in Stroke

Author: Cullell, Natalia, primary, González-Sánchez, Jonathan, additional, Fernández-Cadenas, Israel, additional, and Krupinski, Jerzy, additional
Published: 2019
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20. A multitrait genetic study of hemostatic factors and hemorrhagic transformation after stroke treatment

Author: Gallego-Fábrega, Cristina, Temprano-Sagrera, Gerard, Cárcel-Márquez, Jara, Muiño, Elena, Cullel, Natalia, Lledós, Miquel, Llucià-Carol, Laia, Martín-Campos, Jesús M., Sobrino, Tomás, Castillo, José, Millán, Mónica, Muñoz-Narbona, Lucía, López-Cancio Martínez, Elena, Ribó, Marc, Álvarez-Sabín, José, Jiménez-Conde, Jordi, Roquer, Jaume, Tur, Silvia, Obach, Victor, Arenillas, Juan, Segura, Tomás, Serrano-Heras, Gemma, Martí-Fàbregas, Joan, Freijo Guerrero, María del Mar, Moniche Álvarez, Francisco, Castellanos, María del Mar, Morrison, Alana C., Smith, Nicholas L., de Vries, Paul S., Fernández-Cadenas, Israel, Sabater-Lleal, María, Gallego-Fábrega, Cristina, Temprano-Sagrera, Gerard, Cárcel-Márquez, Jara, Muiño, Elena, Cullel, Natalia, Lledós, Miquel, Llucià-Carol, Laia, Martín-Campos, Jesús M., Sobrino, Tomás, Castillo, José, Millán, Mónica, Muñoz-Narbona, Lucía, López-Cancio Martínez, Elena, Ribó, Marc, Álvarez-Sabín, José, Jiménez-Conde, Jordi, Roquer, Jaume, Tur, Silvia, Obach, Victor, Arenillas, Juan, Segura, Tomás, Serrano-Heras, Gemma, Martí-Fàbregas, Joan, Freijo Guerrero, María del Mar, Moniche Álvarez, Francisco, Castellanos, María del Mar, Morrison, Alana C., Smith, Nicholas L., de Vries, Paul S., Fernández-Cadenas, Israel, and Sabater-Lleal, María
Abstract: [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
Published: 2023

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

Author: Llucià-Carol, Laia, Muiño, Elena, Cullell, Natalia, Cárcel-Márquez, Jara, Lledós, Miquel, Gallego-Fabrega, Cristina, Martin-Campos, Jesús, Martí-Fàbregas, Joan, Aguilera-Simón, Ana, Planas, Anna M, DeDiego, Marta ML, de Felipe Mimbrera, Alicia, 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 E K, Cordioli, Mattia, Delgado, Pilar, Fernández-Cadenas, Israel, Llucià-Carol, Laia, Muiño, Elena, Cullell, Natalia, Cárcel-Márquez, Jara, Lledós, Miquel, Gallego-Fabrega, Cristina, Martin-Campos, Jesús, Martí-Fàbregas, Joan, Aguilera-Simón, Ana, Planas, Anna M, DeDiego, Marta ML, de Felipe Mimbrera, Alicia, 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 E K, 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., SCOPUS: ar.j, info:eu-repo/semantics/published
Published: 2023

22. Host factor PLAC8 is required for pancreas infection by SARS-CoV-2

Author: Ibargüen-González, Lesly, Heller, Sandra, DeDiego, Marta L., López-García, Darío, Gómez-Valero, Alba M., Barth, Thomas F. E., Gallego, Patricia, Fernández-Cadenas, Israel, Alzate-Piñol, Sayoa, Crespí, Catalina, Mena-Guerrero, Julieth A., Cisneros-Barroso, Eugenia, Ugalde, Alejandro P., Bretones, Gabriel, Steenblock, Charlotte, Kleger, Alexander, Barceló, Carles, Ibargüen-González, Lesly, Heller, Sandra, DeDiego, Marta L., López-García, Darío, Gómez-Valero, Alba M., Barth, Thomas F. E., Gallego, Patricia, Fernández-Cadenas, Israel, Alzate-Piñol, Sayoa, Crespí, Catalina, Mena-Guerrero, Julieth A., Cisneros-Barroso, Eugenia, Ugalde, Alejandro P., Bretones, Gabriel, Steenblock, Charlotte, Kleger, Alexander, and Barceló, Carles
Abstract: Although mounting evidence demonstrated that pancreas is infected by SARS-CoV-2 the severity and pathophysiology of pancreatic COVID-19 disease are still unclear. Here we investigated the consequences of SARS-CoV-2 infection of the pancreas and the role of Placenta-associated protein-8 (PLAC8). Our data showed pancreatic damage in patients who died from COVID-19. Notably, circulating pancreatic enzymes stratified patients according to COVID-19 severity and outcome. PLAC8 expression was associated with SARS-CoV-2 infection in postmortem analysis of COVID-19 patients and functional assays demonstrated the requirement of PLAC8 in SARS-CoV-2 pancreatic infection. Full SARS-CoV-2 infectious virus revealed a requirement of PLAC8 for efficient viral infection of pancreatic cell lines. Finally, we observed colocalization of PLAC8 and SARS-CoV-2 in the pancreas of deceased patients. In conclusion, our data confirm the human pancreas as a SARS-CoV-2 target and demonstrate the requirement of PLAC8 for SARS-CoV-2 pancreatic infection thereby opening new target opportunities for COVID-19-associated pancreatic pathogenesis.
Published: 2023

23. Effect of OAS genes on SARS-CoV-2 infection and the induction of innate immune responses

Author: DeDiego, Marta L., López-Fernández, R., López-García, Darío, Nogales, Aitor, Carol, L. L., Pedragosa, Jordi, Durbán, Jordi, Vázquez-Utrilla, P., Rivero, V., Cardona, Fernando, Fernández-Cadenas, Israel, Pérez-Tur, Jordi, Planas, Anna M., DeDiego, Marta L., López-Fernández, R., López-García, Darío, Nogales, Aitor, Carol, L. L., Pedragosa, Jordi, Durbán, Jordi, Vázquez-Utrilla, P., Rivero, V., Cardona, Fernando, Fernández-Cadenas, Israel, Pérez-Tur, Jordi, and Planas, Anna M.
Abstract: Severe Acute Respiratory Syndrome 2 (SARS-CoV-2) infections cause different clinical symptoms ranging from asymptomatic patients to patients suffering severe respiratory disease leading to death in some of them. Genetic and functional studies have shown inborn-errors of interferon (IFN)-related genes in severe COVID-19 patients explaining why some young patients devoid of co-morbidities succumbed to infection. In addition, very large genomic studies identified common genetic variants affecting the expression and splicing of IFN-stimulated genes (ISGs) of the 2",5"- oligoadenylate (2-5A) synthetase (OAS) family associated with COVID-19 severity. We have sequenced the whole genome of 274 patients who required hospitalization after SARS-CoV-2 infection, finding ultrarare mutations in OAS1 and OAS3 genes. Upon double-stranded (ds)RNA binding, the OAS1, OAS2, and OAS3 proteins synthetize 2¿- 5¿olygoadenylates which activate the endonuclease RNAseL. This endonuclease degrades viral and cellular RNAs, inhibiting viral replication. We have analyzed the effect of OAS1 and OAS3 genetic variants identified in our patients, and found that some of them impair the RNAseL activation. In addition, by using OAS3 knock-out cells generated in our laboratory and performing overexpression experiments, we have shown that OAS3 negatively modulates proinflammatory responses induced by immune challenges, and that the activation of the RNAseL activity seems necessary for this function. In addition, by using OAS3 knock-out mice infected with SARS-CoV-2 or treated with the double-stranded RNA analog poly(I:C), we have shown that OAS3 deficiency leads to a higher mouse susceptibility to SARS-CoV-2 infection and that OAS3 counteracts the induction of innate immune responses in the mouse infectedlungs, leading to a higher inflammatory response in OAS3 knock-out mice, compared to the parental mice. Given the contribution of exacerbated inflammatory responses to COVID-19 disease severity, our resul
Published: 2023

24. 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

25. Causal role of lipid metabolome on the risk of ischemic stroke, its etiological subtypes, and long-term outcome: A Mendelian randomization study

Author: Red de Enfermedades Vasculares Cerebrales (España), Instituto de Salud Carlos III, European Commission, Generalitat de Catalunya, Martín-Campos, Jesús M., Cárcel-Márquez, Jara, Llucià-Carol, Laia, Lledós, Miquel, Cullell, Natàlia, Muiño, Elena, Gallego-Fabrega, Cristina, Fernández-Cadenas, Israel, Red de Enfermedades Vasculares Cerebrales (España), Instituto de Salud Carlos III, European Commission, Generalitat de Catalunya, Martín-Campos, Jesús M., Cárcel-Márquez, Jara, Llucià-Carol, Laia, Lledós, Miquel, Cullell, Natàlia, Muiño, Elena, Gallego-Fabrega, Cristina, and Fernández-Cadenas, Israel
Abstract: The lipid profile is consistently associated with coronary artery disease (CAD) and ischemic stroke (IS). However, the lipoprotein subfractions have not been deeply explored in stroke subtypes, especially in IS outcome.
Published: 2023

26. Identification of Plasma Biomarkers of Human Intracerebral Hemorrhage Subtypes through Microarray Technology

Author: Merino-Zamorano, Cristina, Delgado, Pilar, Fernández de Retana, Sofía, Fernández-Cadenas, Israel, Rodríguez-Luna, David, Montaner, Joan, and Hernández-Guillamon, Mar
Published: 2016
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27. Validation of a clinical-genetics score to predict hemorrhagic transformations after rtPA

Author: Carrera, Caty, Cullell, Natalia, Torres-Águila, Nuria, Muiño, Elena, Bustamante, Alejandro, Dávalos, Antonio, López-Cancio, Elena, Ribó, Marc, Molina, Carlos A., Giralt-Steinhauer, Eva, Soriano-Tárraga, Carolina, Mola-Caminal, Marina, Jiménez-Conde, Jordi, Roquer, Jaume, Vives-Bauza, Cristófol, Navarro, Rosa Díaz, Obach, Victor, Arenillas, Juan Francisco, Segura, Tomás, Serrano-Heras, Gemma, Martí-Fàbregas, Joan, Freijo, Marimar, Cabezas, Juan Antonio, Tatlisumak, Turgut, Heitsch, Laura, Ibañez, Laura, Cruchaga, Carlos, Lee, Jin-Moo, Strbian, Daniel, Montaner, Joan, and Fernández-Cadenas, Israel
Published: 2019
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28. PATJ Low Frequency Variants Are Associated With Worse Ischemic Stroke Functional Outcome: 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, Natàlia, Torres-Aguila, Nuria P., Muiño, Elena, Rodríguez-Campello, Ana, Ois, Angel, Cuadrado-Godia, Elisa, Vivanco-Hidalgo, Rosa M., Hernandez-Guillamon, Mar, Solé, Montse, Delgado, Pilar, Bustamante, Alejandro, García-Berrocoso, Teresa, Mendióroz, Maite, Castellanos, Mar, Serena, Joaquín, Martí-Fàbregas, Joan, Segura, Tomás, Serrano-Heras, Gemma, Obach, Victor, Ribó, Marc, Molina, Carlos A., Alvarez-Sabín, José, Palomeras, Ernest, Freijo, Mar, Font, Maria A., Rosand, Jonathan, Rost, Natalia S., Gallego-Fabrega, Cristina, Lee, Jin-Moo, Heitsch, Laura, Ibanez, Laura, Cruchaga, Carlos, Phuah, Chia-Ling, Lemmens, Robin, Thijs, Vincent, Lindgren, Arne, Maguire, Jane, Rannikmae, Kristiina, 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, and Jiménez-Conde, Jordi
Published: 2019
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29. Age-dependent impact of the major common genetic risk factor for COVID-19 on severity and mortality

Author: NordForsk, Academy of Finland, Canadian Institutes of Health Research, Lady Davis Institute, Canada Foundation for Innovation, Cancer Research UK, National Institutes of Health (US), Genome Canada, Japan Society for the Promotion of Science, European Commission, Medical Research Council (UK), National Institute for Health Research (UK), Wellcome Trust, German Research Foundation, Federal Ministry of Education and Research (Germany), Instituto de Salud Carlos III, Junta de Andalucía, Columbia University, Università degli Studi di Siena, Ministero della Salute, Consejo Superior de Investigaciones Científicas (España), Swedish Research Council, Technical University of Munich, University of Helsinki, Nakanishi, Tomoko [0000-0001-9510-5646], Pigazzini, Sara [0000-0002-0641-9393], Cordioli, Mattia [0000-0002-4872-0520], Butler-Laporte, Guillaume [0000-0001-5388-0396], Maya-Miles, Douglas [0000-0002-0669-6526], Nafria Jimenez, Beatriz [0000-0002-4698-5680], Bouysran, Youssef [0000-0003-1368-6550], Niemi, Mari [0000-0003-0696-6175], Palom, Adriana [0000-0002-0130-1302], Ellinghaus, David [0000-0002-4332-6110], Khan, Atlas [0000-0002-6651-2725], Martínez-Bueno, Manuel [0000-0002-4333-4487], Roade, Luisa [0000-0002-8160-9613], Fava, Francesca [0000-0002-4363-2353], Spinner, Christoph D. [0000-0002-3875-5367], Prati, Daniele [0000-0002-2281-7498], Bernardo, David [0000-0002-2843-6696], Darcis, Gilles [0000-0001-8192-1351], Fernández-Cadenas, Israel [0000-0003-4821-2363], Holter, Jan Cato [0000-0003-1618-5022], Frithiof, Robert [0000-0003-2278-7951], Kiryluk, Krzysztof [0000-0002-5047-6715], Duga, Stefano [0000-0003-3457-1410], Asselta, Rosanna [0000-0001-5351-0619], Pereira, Alexandre [0000-0002-7782-5540], Romero-Gómez, Manuel [0000-0001-8494-8947], Hov, Johannes R. [0000-0002-5900-8096], Migeotte, Isabelle [0000-0002-8972-8211], Renieri, Alessandra [0000-0002-0846-9220], Planas, Anna M. [0000-0002-6147-1880], Ludwig, Kerstin [0000-0002-8541-2519], Buti, María [0000-0002-0732-3078], Rahmouni, Souad [0000-0003-0956-0242], Alarcón-Riquelme, M. E. [0000-0002-7632-4154], Schulte, Eva C. [0000-0003-3105-5672], Karlsen, Tom H. [0000-0002-8289-9931], Valenti, Luca [0000-0001-8909-0345], Zeberg, Hugo [0000-0001-7118-1249], Richards, Brent [0000-0002-3746-9086], Ganna, Andrea [0000-0002-8147-240X], Nakanishi, Tomoko, Pigazzini, Sara, Degenhardt, Frauke, Cordioli, Mattia, Butler-Laporte, Guillaume, Maya-Miles, Douglas, Nafría-Jiménez, Beatriz, Bouysran, Youssef, Niemi, Mari, Palom, Adriana, Ellinghaus, David, Khan, Atlas, Martínez-Bueno, Manuel, Rolker, Selina, Amitano, Sara, Roade, Luisa, FinnGen, The COVID-19 Host Genetics Initiative, Fava, Francesca, Spinner, Christoph D., Prati, Daniele, Bernardo, David, García, Federico, Darcis, Gilles, Fernández-Cadenas, Israel, Holter, Jan Cato, Banales, Jesús M., Frithiof, Robert, Kiryluk, Krzysztof, Duga, Stefano, Asselta, Rosanna, Pereira, Alexandre, Romero-Gómez, Manuel, Bujanda, Luis, Hov, Johannes R., Migeotte, Isabelle, Renieri, Alessandra, Planas, Anna M., Ludwig, Kerstin, Buti, María, Rahmouni, Souad, Alarcón-Riquelme, Marta E., Schulte, Eva C., Franke, Andre, Karlsen, Tom H., Valenti, Luca, Zeberg, Hugo, Richards, Brent, Ganna, Andrea, NordForsk, Academy of Finland, Canadian Institutes of Health Research, Lady Davis Institute, Canada Foundation for Innovation, Cancer Research UK, National Institutes of Health (US), Genome Canada, Japan Society for the Promotion of Science, European Commission, Medical Research Council (UK), National Institute for Health Research (UK), Wellcome Trust, German Research Foundation, Federal Ministry of Education and Research (Germany), Instituto de Salud Carlos III, Junta de Andalucía, Columbia University, Università degli Studi di Siena, Ministero della Salute, Consejo Superior de Investigaciones Científicas (España), Swedish Research Council, Technical University of Munich, University of Helsinki, Nakanishi, Tomoko [0000-0001-9510-5646], Pigazzini, Sara [0000-0002-0641-9393], Cordioli, Mattia [0000-0002-4872-0520], Butler-Laporte, Guillaume [0000-0001-5388-0396], Maya-Miles, Douglas [0000-0002-0669-6526], Nafria Jimenez, Beatriz [0000-0002-4698-5680], Bouysran, Youssef [0000-0003-1368-6550], Niemi, Mari [0000-0003-0696-6175], Palom, Adriana [0000-0002-0130-1302], Ellinghaus, David [0000-0002-4332-6110], Khan, Atlas [0000-0002-6651-2725], Martínez-Bueno, Manuel [0000-0002-4333-4487], Roade, Luisa [0000-0002-8160-9613], Fava, Francesca [0000-0002-4363-2353], Spinner, Christoph D. [0000-0002-3875-5367], Prati, Daniele [0000-0002-2281-7498], Bernardo, David [0000-0002-2843-6696], Darcis, Gilles [0000-0001-8192-1351], Fernández-Cadenas, Israel [0000-0003-4821-2363], Holter, Jan Cato [0000-0003-1618-5022], Frithiof, Robert [0000-0003-2278-7951], Kiryluk, Krzysztof [0000-0002-5047-6715], Duga, Stefano [0000-0003-3457-1410], Asselta, Rosanna [0000-0001-5351-0619], Pereira, Alexandre [0000-0002-7782-5540], Romero-Gómez, Manuel [0000-0001-8494-8947], Hov, Johannes R. [0000-0002-5900-8096], Migeotte, Isabelle [0000-0002-8972-8211], Renieri, Alessandra [0000-0002-0846-9220], Planas, Anna M. [0000-0002-6147-1880], Ludwig, Kerstin [0000-0002-8541-2519], Buti, María [0000-0002-0732-3078], Rahmouni, Souad [0000-0003-0956-0242], Alarcón-Riquelme, M. E. [0000-0002-7632-4154], Schulte, Eva C. [0000-0003-3105-5672], Karlsen, Tom H. [0000-0002-8289-9931], Valenti, Luca [0000-0001-8909-0345], Zeberg, Hugo [0000-0001-7118-1249], Richards, Brent [0000-0002-3746-9086], Ganna, Andrea [0000-0002-8147-240X], Nakanishi, Tomoko, Pigazzini, Sara, Degenhardt, Frauke, Cordioli, Mattia, Butler-Laporte, Guillaume, Maya-Miles, Douglas, Nafría-Jiménez, Beatriz, Bouysran, Youssef, Niemi, Mari, Palom, Adriana, Ellinghaus, David, Khan, Atlas, Martínez-Bueno, Manuel, Rolker, Selina, Amitano, Sara, Roade, Luisa, FinnGen, The COVID-19 Host Genetics Initiative, Fava, Francesca, Spinner, Christoph D., Prati, Daniele, Bernardo, David, García, Federico, Darcis, Gilles, Fernández-Cadenas, Israel, Holter, Jan Cato, Banales, Jesús M., Frithiof, Robert, Kiryluk, Krzysztof, Duga, Stefano, Asselta, Rosanna, Pereira, Alexandre, Romero-Gómez, Manuel, Bujanda, Luis, Hov, Johannes R., Migeotte, Isabelle, Renieri, Alessandra, Planas, Anna M., Ludwig, Kerstin, Buti, María, Rahmouni, Souad, Alarcón-Riquelme, Marta E., Schulte, Eva C., Franke, Andre, Karlsen, Tom H., Valenti, Luca, Zeberg, Hugo, Richards, Brent, and Ganna, Andrea
Abstract: Background There is considerable variability in COVID-19 outcomes amongst younger adults—and some of this variation may be due to genetic predisposition. We characterized the clinical implications of the major genetic risk factor for COVID-19 severity, and its age-dependent effect, using individual-level data in a large international multi-centre consortium. Method The major common COVID-19 genetic risk factor is a chromosome 3 locus, tagged by the marker rs10490770. We combined individual level data for 13,424 COVID-19 positive patients (N=6,689 hospitalized) from 17 cohorts in nine countries to assess the association of this genetic marker with mortality, COVID-19-related complications and laboratory values. We next examined if the magnitude of these associations varied by age and were independent from known clinical COVID-19 risk factors. Findings We found that rs10490770 risk allele carriers experienced an increased risk of all-cause mortality (hazard ratio [HR] 1·4, 95% confidence interval [CI] 1·2–1·6) and COVID-19 related mortality (HR 1·5, 95%CI 1·3–1·8). Risk allele carriers had increased odds of several COVID-19 complications: severe respiratory failure (odds ratio [OR] 2·0, 95%CI 1·6-2·6), venous thromboembolism (OR 1·7, 95%CI 1·2-2·4), and hepatic injury (OR 1·6, 95%CI 1·2-2·0). Risk allele carriers ≤ 60 years had higher odds of death or severe respiratory failure (OR 2·6, 95%CI 1·8-3·9) compared to those > 60 years OR 1·5 (95%CI 1·3-1·9, interaction p-value=0·04). Amongst individuals ≤ 60 years who died or experienced severe respiratory COVID-19 outcome, we found that 31·8% (95%CI 27·6-36·2) were risk variant carriers, compared to 13·9% (95%CI 12·6-15·2%) of those not experiencing these outcomes. Prediction of death or severe respiratory failure among those ≤ 60 years improved when including the risk allele (AUC 0·82 vs 0·84, p=0·016) and the prediction ability of rs10490770 risk allele was similar to, or better than, most established clinical risk fact
Published: 2021

30. Age-dependent impact of the major common genetic risk factor for COVID-19 on severity and mortality

Author: Nakanishi, Tomoko, Pigazzini, Sara, Degenhardt, Frauke, Cordioli, Mattia, Butler-Laporte, Guillaume, Maya-Miles, Douglas, Nafria Jimenez, Beatriz, Bouysran, Youssef, Niemi, Mari, Palom, Adriana, Ellinghaus, David, Khan, Atlas, Martínez-Bueno, Manuel, Rolker, Selina, Amitano, Sara, Roade, Luisa, FinnGen, The COVID-19 Host Genetics Initiative, Fava, Francesca, Spinner, Christoph D., Prati, Daniele, Bernardo, David, García, Federico, Darcis, Gilles, Fernández-Cadenas, Israel, Holter, Jan Cato, Banales, Jesús M., Frithiof, Robert, Kiryluk, Krzysztof, Duga, Stefano, Asselta, Rosanna, Pereira, Alexandre, Romero-Gómez, Manuel, Bujanda, Luis, Hov, Johannes R., Migeotte, Isabelle, Renieri, Alessandra, Planas, Anna M., Ludwig, Kerstin, Buti, María, Rahmouni, Souad, Alarcón-Riquelme, Marta E., Schulte, Eva C., Franke, Andre, Karlsen, Tom H., Valenti, Luca, Zeberg, Hugo, Richards, Brent, Ganna, Andrea, NordForsk, Academy of Finland, Canadian Institutes of Health Research, Lady Davis Institute, Canada Foundation for Innovation, Cancer Research UK, National Institutes of Health (US), Genome Canada, Japan Society for the Promotion of Science, European Commission, Medical Research Council (UK), National Institute for Health Research (UK), Wellcome Trust, German Research Foundation, Federal Ministry of Education and Research (Germany), Instituto de Salud Carlos III, Junta de Andalucía, Columbia University, Università degli Studi di Siena, Ministero della Salute, Consejo Superior de Investigaciones Científicas (España), Swedish Research Council, Technical University of Munich, University of Helsinki, Nakanishi, Tomoko [0000-0001-9510-5646], Pigazzini, Sara [0000-0002-0641-9393], Cordioli, Mattia [0000-0002-4872-0520], Butler-Laporte, Guillaume [0000-0001-5388-0396], Maya-Miles, Douglas [0000-0002-0669-6526], Nafria Jimenez, Beatriz [0000-0002-4698-5680], Bouysran, Youssef [0000-0003-1368-6550], Niemi, Mari [0000-0003-0696-6175], Palom, Adriana [0000-0002-0130-1302], Ellinghaus, David [0000-0002-4332-6110], Khan, Atlas [0000-0002-6651-2725], Martínez-Bueno, Manuel [0000-0002-4333-4487], Roade, Luisa [0000-0002-8160-9613], Fava, Francesca [0000-0002-4363-2353], Spinner, Christoph D. [0000-0002-3875-5367], Prati, Daniele [0000-0002-2281-7498], Bernardo, David [0000-0002-2843-6696], Darcis, Gilles [0000-0001-8192-1351], Fernández-Cadenas, Israel [0000-0003-4821-2363], Holter, Jan Cato [0000-0003-1618-5022], Frithiof, Robert [0000-0003-2278-7951], Kiryluk, Krzysztof [0000-0002-5047-6715], Duga, Stefano [0000-0003-3457-1410], Asselta, Rosanna [0000-0001-5351-0619], Pereira, Alexandre [0000-0002-7782-5540], Romero-Gómez, Manuel [0000-0001-8494-8947], Hov, Johannes R. [0000-0002-5900-8096], Migeotte, Isabelle [0000-0002-8972-8211], Renieri, Alessandra [0000-0002-0846-9220], Planas, Anna M. [0000-0002-6147-1880], Ludwig, Kerstin [0000-0002-8541-2519], Buti, María [0000-0002-0732-3078], Rahmouni, Souad [0000-0003-0956-0242], Alarcón-Riquelme, M. E. [0000-0002-7632-4154], Schulte, Eva C. [0000-0003-3105-5672], Karlsen, Tom H. [0000-0002-8289-9931], Valenti, Luca [0000-0001-8909-0345], Zeberg, Hugo [0000-0001-7118-1249], Richards, Brent [0000-0002-3746-9086], Ganna, Andrea [0000-0002-8147-240X], Junta de Castilla y León, Fundació Glòria Soler, Swedish Kidney Foundation, Research Council of Norway, Nakanishi, Tomoko, Pigazzini, Sara, Cordioli, Mattia, Butler-Laporte, Guillaume, Maya-Miles, Douglas, Nafria Jimenez, Beatriz, Bouysran, Youssef, Niemi, Mari, Palom, Adriana, Ellinghaus, David, Khan, Atlas, Martínez-Bueno, Manuel, Roade, Luisa, Fava, Francesca, Spinner, Christoph D., Prati, Daniele, Bernardo, David, Darcis, Gilles, Fernández-Cadenas, Israel, Holter, Jan Cato, Frithiof, Robert, Kiryluk, Krzysztof, Duga, Stefano, Asselta, Rosanna, Pereira, Alexandre, Romero-Gómez, Manuel, Hov, Johannes R., Migeotte, Isabelle, Renieri, Alessandra, Planas, Anna M., Ludwig, Kerstin, Buti, María, Rahmouni, Souad, Alarcón-Riquelme, M. E., Schulte, Eva C., Karlsen, Tom H., Valenti, Luca, Zeberg, Hugo, Richards, Brent, Ganna, Andrea, Nakanishi, T., Pigazzini, S., Degenhardt, F., Cordioli, M., Butler-Laporte, G., Maya-Miles, D., Bujanda, L., Bouysran, Y., Niemi, M. E. K., Palom, A., Ellinghaus, D., Khan, A., Martinez-Bueno, M., Rolker, S., Amitrano, S., Tato, L. R., Fava, F., Gen, F., Spinner, C. D., Prati, D., Bernardo, D., Garcia, F., Darcis, G., Fernandez-Cadenas, I., Holter, J. C., Banales, J. M., Frithiof, R., Kiryluk, K., Duga, S., Asselta, R., Pereira, A. C., Romero-Gomez, M., Nafria-Jimenez, B., Hov, J. R., Migeotte, I., Renieri, A., Planas, A. M., Ludwig, K. U., Buti, M., Rahmouni, S., Alarcon-Riquelme, M. E., Schulte, E. C., Franke, A., Karlsen, T. H., Valenti, L., Zeberg, H., Richards, J. B., and Ganna, A.
Subjects: Male, Coronavirus disease 2019 (COVID-19), Age dependent, Article, 03 medical and health sciences, 0302 clinical medicine, Genetic, Gene Frequency, Risk Factors, Genetics, Medicine, Humans, Age Factor, Genetic variation, 030212 general & internal medicine, Respiratory system, Alleles, 030304 developmental biology, Aged, Allele, Aged, 80 and over, 0303 health sciences, Polymorphism, Genetic, business.industry, SARS-CoV-2, Risk Factor, Hazard ratio, Age Factors, Patient Acuity, COVID-19, Odds ratio, Covid-19, Genetic Variation, Sciences bio-médicales et agricoles, Middle Aged, COVID-19 (Enfermedad), Confidence interval, 3. Good health, Genetic Loci, Commentary, Female, Chromosomes, Human, Pair 3, Genetic risk factor, business, Venous thromboembolism, Human, Demography
Abstract: AG has received support by NordForsk Nordic Trial Alliance (NTA) grant, by Academy of Finland Fellow grant N. 323116 and the Academy of Finland for PREDICT consortium N. 340541. The Richards research group is supported by the Canadian Institutes of Health Research (CIHR) (365825 and 409511), the Lady Davis Institute of the Jewish General Hospital, the Canadian Foundation for Innovation (CFI), the NIH Foundation, Cancer Research UK, Genome Québec, the Public Health Agency of Canada, the McGill Interdisciplinary Initiative in Infection and Immunity and the Fonds de Recherche Québec Santé (FRQS). TN is supported by a research fellowship of the Japan Society for the Promotion of Science for Young Scientists. GBL is supported by a CIHR scholarship and a joint FRQS and Québec Ministry of Health and Social Services scholarship. JBR is supported by an FRQS Clinical Research Scholarship. Support from Calcul Québec and Compute Canada is acknowledged. TwinsUK is funded by the Welcome Trust, the Medical Research Council, the European Union, the National Institute for Health Research-funded BioResource and the Clinical Research Facility and Biomedical Research Centre based at Guy’s and St. Thomas’ NHS Foundation Trust in partnership with King’s College London. The Biobanque Québec COVID19 is funded by FRQS, Genome Québec and the Public Health Agency of Canada, the McGill Interdisciplinary Initiative in Infection and Immunity and the Fonds de Recherche Québec Santé. These funding agencies had no role in the design, implementation or interpretation of this study. The COVID19-Host(a)ge study received infrastructure support from the DFG Cluster of Excellence 2167 “Precision Medicine in Chronic Inflammation (PMI)” (DFG Grant: “EXC2167”). The COVID19-Host(a)ge study was supported by the German Federal Ministry of Education and Research (BMBF) within the framework of the Computational Life Sciences funding concept (CompLS grant 031L0165). Genotyping in COVID19-Host(a)ge was supported by a philantropic donation from Stein Erik Hagen. The COVID GWAs, Premed COVID-19 study (COVID19-Host(a)ge_3) was supported by "Grupo de Trabajo en Medicina Personalizada contra el COVID-19 de Andalucia"and also by the Instituto de Salud Carlos III (CIBERehd and CIBERER). Funding comes from COVID-19-GWAS, COVID-PREMED initiatives. Both of them are supported by "Consejeria de Salud y Familias" of the Andalusian Government. DMM is currently funded by the the Andalussian government (Proyectos Estratégicos-Fondos Feder PE-0451-2018). The Columbia University Biobank was supported by Columbia University and the National Center for Advancing Translational Sciences, NIH, through Grant Number UL1TR001873. The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH or Columbia University. The SPGRX study was supported by the Consejería de Economía, Conocimiento, Empresas y Universidad #CV20-10150. The GEN-COVID study was funded by: the MIUR grant “Dipartimenti di Eccellenza 2018-2020” to the Department of Medical Biotechnologies University of Siena, Italy; the “Intesa San Paolo 2020 charity fund” dedicated to the project NB/2020/0119; and philanthropic donations to the Department of Medical Biotechnologies, University of Siena for the COVID-19 host genetics research project (D.L n.18 of March 17, 2020). Part of this research project is also funded by Tuscany Region “Bando Ricerca COVID-19 Toscana” grant to the Azienda Ospedaliero Universitaria Senese (CUP I49C20000280002). Authors are grateful to: the CINECA consortium for providing computational resources; the Network for Italian Genomes (NIG) (http://www.nig.cineca.it) for its support; the COVID-19 Host Genetics Initiative (https://www.covid19hg.org/); the Genetic Biobank of Siena, member of BBMRI-IT, Telethon Network of Genetic Biobanks (project no. GTB18001), EuroBioBank, and RD-Connect, for managing specimens. Genetics against coronavirus (GENIUS), Humanitas University (COVID19-Host(a)ge_4) was supported by Ricerca Corrente (Italian Ministry of Health), intramural funding (Fondazione Humanitas per la Ricerca). The generous contribution of Banca Intesa San Paolo and of the Dolce&Gabbana Fashion Firm is gratefully acknowledged. Data acquisition and sample processing was supported by COVID-19 Biobank, Fondazione IRCCS Cà Granda Milano; LV group was supported by MyFirst Grant AIRC n.16888, Ricerca Finalizzata Ministero della Salute RF-2016-02364358, Ricerca corrente Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico, the European Union (EU) Programme Horizon 2020 (under grant agreement No. 777377) for the project LITMUS- “Liver Investigation: Testing Marker Utility in Steatohepatitis”, Programme “Photonics” under grant agreement “101016726” for the project “REVEAL: Neuronal microscopy for cell behavioural examination and manipulation”, Fondazione Patrimonio Ca’ Granda “Liver Bible” PR-0361. DP was supported by Ricerca corrente Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico, CV PREVITAL “Strategie di prevenzione primaria nella popolazione Italiana” Ministero della Salute, and Associazione Italiana per la Prevenzione dell’Epatite Virale (COPEV). Genetic modifiers for COVID-19 related illness (BeLCovid_1) was supported by the "Fonds Erasme". The Host genetics and immune response in SARS-Cov-2 infection (BelCovid_2) study was supported by grants from Fondation Léon Fredericq and from Fonds de la Recherche Scientifique (FNRS). The INMUNGEN-CoV2 study was funded by the Consejo Superior de Investigaciones Científicas. KUL is supported by the German Research Foundation (LU 1944/3-1) SweCovid is funded by the SciLifeLab/KAW national COVID-19 research program project grant to Michael Hultström (KAW 2020.0182) and the Swedish Research Council to Robert Frithiof (2014-02569 and 2014-07606). HZ is supported by Jeansson Stiftelser, Magnus Bergvalls Stiftelse. The COMRI cohort is funded by Technical University of Munich, Munich, Germany. Genotyping for the COMRI cohort was performed and funded by the Genotyping Laboratory of Institute for Molecular Medicine Finland FIMM Technology Centre, University of Helsinki, Helsinki, Finland. These funding agencies had no role in the design, implementation or interpretation of this study., Background: There is considerable variability in COVID-19 outcomes amongst younger adults—and some of this variation may be due to genetic predisposition. We characterized the clinical implications of the major genetic risk factor for COVID-19 severity, and its age-dependent effect, using individual-level data in a large international multi-centre consortium. Method: The major common COVID-19 genetic risk factor is a chromosome 3 locus, tagged by the marker rs10490770. We combined individual level data for 13,424 COVID-19 positive patients (N=6,689 hospitalized) from 17 cohorts in nine countries to assess the association of this genetic marker with mortality, COVID-19-related complications and laboratory values. We next examined if the magnitude of these associations varied by age and were independent from known clinical COVID-19 risk factors. Findings: We found that rs10490770 risk allele carriers experienced an increased risk of all-cause mortality (hazard ratio [HR] 1·4, 95% confidence interval [CI] 1·2–1·6) and COVID-19 related mortality (HR 1·5, 95%CI 1·3–1·8). Risk allele carriers had increased odds of several COVID-19 complications: severe respiratory failure (odds ratio [OR] 2·0, 95%CI 1·6-2·6), venous thromboembolism (OR 1·7, 95%CI 1·2-2·4), and hepatic injury (OR 1·6, 95%CI 1·2-2·0). Risk allele carriers ≤ 60 years had higher odds of death or severe respiratory failure (OR 2·6, 95%CI 1·8-3·9) compared to those > 60 years OR 1·5 (95%CI 1·3-1·9, interaction p-value=0·04). Amongst individuals ≤ 60 years who died or experienced severe respiratory COVID-19 outcome, we found that 31·8% (95%CI 27·6-36·2) were risk variant carriers, compared to 13·9% (95%CI 12·6-15·2%) of those not experiencing these outcomes. Prediction of death or severe respiratory failure among those ≤ 60 years improved when including the risk allele (AUC 0·82 vs 0·84, p=0·016) and the prediction ability of rs10490770 risk allele was similar to, or better than, most established clinical risk factors. Interpretation: The major common COVID-19 risk locus on chromosome 3 is associated with increased risks of morbidity and mortality—and these are more pronounced amongst individuals ≤ 60 years. The effect on COVID-19 severity was similar to, or larger than most established risk factors, suggesting potential implications for clinical risk management., Academy of Finland Fellow grant N. 323116, Academy of Finland for PREDICT consortium N. 340541., Canadian Institutes of Health Research (CIHR) (365825 and 409511), Lady Davis Institute of the Jewish General Hospital, Canadian Foundation for Innovation (CFI), NIH Foundation, Cancer Research UK, Genome Québec, Public Health Agency of Canada, McGill Interdisciplinary Initiative in Infection and Immunity and the Fonds de Recherche Québec Santé (FRQS), Japan Society for the Promotion of Science for Young Scientists, CIHR scholarship and a joint FRQS and Québec Ministry of Health and Social Services scholarship, FRQS Clinical Research Scholarship, Calcul Québec, Compute Canada, Welcome Trust, Medical Research Counc, European Union, National Institute for Health Research-funded BioResource, Clinical Research Facility and Biomedical Research Centre based at Guy’s and St. Thomas’ NHS Foundation Trust, King’s College London, McGill Interdisciplinary Initiative in Infection and Immunity, Fonds de Recherche Québec Santé, (DFG Grant: “EXC2167”), (CompLS grant 031L0165), Stein Erik Hagen, "Grupo de Trabajo en Medicina Personalizada contra el COVID-19 de Andalucia", Instituto de Salud Carlos III (CIBERehd and CIBERER), COVID-19-GWAS, COVID-PREMED initiatives, "Consejeria de Salud y Familias" of the Andalusian Government, Andalusian government (Proyectos Estratégicos-Fondos Feder PE-0451-2018), Columbia University, National Center for Advancing Translational Sciences, NIH Grant Number UL1TR001873, Consejería de Economía, Conocimiento, Empresas y Universidad #CV20-10150, MIUR grant “Dipartimenti di Eccellenza 2018-2020”, “Intesa San Paolo 2020 charity fund” dedicated to the project NB/2020/0119, Tuscany Region “Bando Ricerca COVID-19 Toscana”, CINECA consortium, Network for Italian Genomes (NIG), COVID-19 Host Genetics Initiative, Genetic Biobank of Siena, EuroBioBank, RD-Connect, Ricerca Corrente (Italian Ministry of Health), Fondazione Humanitas per la Ricerca, Banca Intesa San Paolo, Dolce&Gabbana Fashion Firm, COVID-19 Biobank, Fondazione IRCCS Cà Granda Milano, MyFirst Grant AIRC n.16888, Ricerca Finalizzata Ministero della Salute RF-2016-02364358, Ricerca corrente Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico, European Union (EU) Programme Horizon 2020 (under grant agreement No. 777377), “Photonics” “101016726”, Fondazione Patrimonio Ca’ Granda “Liver Bible” PR-0361, CV PREVITAL “Strategie di prevenzione primaria nella popolazione Italiana” Ministero della Salute, and Associazione Italiana per la Prevenzione dell’Epatite Virale (COPEV), "Fonds Erasme", Fondation Léon Fredericq, Fonds de la Recherche Scientifique (FNRS), Consejo Superior de Investigaciones Científicas, German Research Foundation (LU 1944/3-1), SciLifeLab/KAW national COVID-19 research program project (KAW 2020.0182), Swedish Research Council (2014-02569 and 2014-07606), Jeansson Stiftelser, Magnus Bergvalls Stiftelse, Technical University of Munich, Munich, Germany, Genotyping Laboratory of Institute for Molecular Medicine Finland FIMM Technology Centre, University of Helsinki, Helsinki, Finland
Published: 2021
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31. Biological Age Acceleration Is Lower in Women With Ischemic Stroke Compared to Men

Author: Gallego-Fabrega, Cristina, primary, Muiño, Elena, additional, Cullell, Natalia, additional, Cárcel-Márquez, Jara, additional, Lazcano, Uxue, additional, Soriano-Tárraga, Carolina, additional, Lledós, Miquel, additional, Llucià-Carol, Laia, additional, Aguilera-Simón, Ana, additional, Marín, Rebeca, additional, Prats-Sánchez, Luis, additional, Camps-Renom, Pol, additional, Delgado-Mederos, Raquel, additional, Martín-Campos, Jesús M., additional, Delgado, Pilar, additional, Martí-Fàbregas, Joan, additional, Montaner, Joan, additional, Krupinski, Jerzy, additional, Jiménez-Conde, J., additional, Roquer, Jaume, additional, and Fernández-Cadenas, Israel, additional
Published: 2022
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32. Genome-Wide Studies in Ischaemic Stroke: Are Genetics Only Useful for Finding Genes?

Author: Gallego-Fabrega, Cristina, primary, Muiño, Elena, additional, Cárcel-Márquez, Jara, additional, Llucià-Carol, Laia, additional, Lledós, Miquel, additional, Martín-Campos, Jesús M., additional, Cullell, Natalia, additional, and Fernández-Cadenas, Israel, additional
Published: 2022
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33. DNA Methylation and Ischemic Stroke Risk: An Epigenome-Wide Association Study

Author: Cullell, Natalia, additional, Soriano-Tárraga, Carolina, additional, Gallego-Fábrega, Cristina, additional, Cárcel-Márquez, Jara, additional, Torres-Águila, Nuria P., additional, Muiño, Elena, additional, Lledós, Miquel, additional, Llucià-Carol, Laia, additional, Esteller, Manel, additional, Castro de Moura, Manuel, additional, Montaner, Joan, additional, Fernández-Sanlés, Alba, additional, Elosua, Roberto, additional, Delgado, Pilar, additional, Martí-Fábregas, Joan, additional, Krupinski, Jerzy, additional, Roquer, Jaume, additional, Jiménez-Conde, Jordi, additional, and Fernández-Cadenas, Israel, additional
Published: 2022
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34. Novel genes and sex differences in COVID-19 severity

Author: Cruz, Raquel, Diz-de Almeida, Silvia, López de Heredia, Miguel, Quintela, Inés, Ceballos, Francisco C, Pita, Guillermo, Lorenzo-Salazar, José M, González-Montelongo, Rafaela, Gago-Domínguez, Manuela, Sevilla Porras, Marta, Tenorio Castaño, Jair Antonio, Nevado, Julian, Aguado, Jose María, Aguilar, Carlos, Aguilera-Albesa, Sergio, Almadana, Virginia, Almoguera, Berta, Alvarez, Nuria, Andreu-Bernabeu, Álvaro, Arana-Arri, Eunate, Arango, Celso, Arranz, María J, Artiga, Maria-Jesus, Baptista-Rosas, Raúl C, Barreda-Sánchez, María, Belhassen-Garcia, Moncef, Bezerra, Joao F, Bezerra, Marcos A C, Boix-Palop, Lucía, Brion, María, Brugada, Ramón, Bustos, Matilde, Calderón, Enrique J, Carbonell, Cristina, Castano, Luis, Castelao, Jose E, Conde-Vicente, Rosa, Cordero-Lorenzana, M Lourdes, Cortes-Sanchez, Jose L, Corton, Marta, Darnaude, M Teresa, De Martino-Rodríguez, Alba, Del Campo-Pérez, Victor, Diaz de Bustamante, Aranzazu, Domínguez-Garrido, Elena, Luchessi, Andre D, Eiros, Rocío, Estigarribia Sanabria, Gladys Mercedes, Carmen Fariñas, María, Fernández-Robelo, Uxía, Fernández-Rodríguez, Amanda, Fernández-Villa, Tania, Gil-Fournier, Belén, Gómez-Arrue, Javier, González Álvarez, Beatriz, Gonzalez Bernaldo de Quirós, Fernan, González-Peñas, Javier, Gutiérrez-Bautista, Juan F, Herrero, María José, Herrero-Gonzalez, Antonio, Jimenez-Sousa, María A, Lattig, María Claudia, Liger Borja, Anabel, Lopez-Rodriguez, Rosario, Mancebo, Esther, Martín-López, Caridad, Martín, Vicente, Martinez-Nieto, Oscar, Martinez-Lopez, Iciar, Martinez-Resendez, Michel F, Martinez-Perez, Angel, Mazzeu, Juliana F, Merayo Macías, Eleuterio, Minguez, Pablo, Moreno Cuerda, Victor, Silbiger, Vivian N, Oliveira, Silviene F, Ortega-Paino, Eva, Parellada, Mara, Paz-Artal, Estela, Santos, Ney P C, Pérez-Matute, Patricia, Perez, Patricia, Pérez-Tomás, M Elena, Perucho, Teresa, Pinsach-Abuin, Mel Lina, Pompa-Mera, Ericka N, Porras-Hurtado, Gloria L, Pujol, Aurora, Ramiro León, Soraya, Resino, Salvador, Fernandes, Marianne R, Rodríguez-Ruiz, Emilio, Rodriguez-Artalejo, Fernando, Rodriguez-Garcia, José A, Ruiz Cabello, Francisco, Ruiz-Hornillos, Javier, Ryan, Pablo, Soria, José Manuel, Souto, Juan Carlos, Tamayo, Eduardo, Tamayo-Velasco, Alvaro, Taracido-Fernandez, Juan Carlos, Teper, Alejandro, Torres-Tobar, Lilian, Urioste, Miguel, Valencia-Ramos, Juan, Yáñez, Zuleima, Zarate, Ruth, Nakanishi, Tomoko, Pigazzini, Sara, Degenhardt, Frauke, Butler-Laporte, Guillaume, Maya-Miles, Douglas, Bujanda, Luis, Bouysran, Youssef, Palom, Adriana, Ellinghaus, David, Martínez-Bueno, Manuel, Rolker, Selina, Amitrano, Sara, Roade, Luisa, Fava, Francesca, Spinner, Christoph D, Prati, Daniele, Bernardo, David, Garcia, Federico, Darcis, Gilles, Fernández-Cadenas, Israel, Holter, Jan Cato, Banales, Jesus M, Frithiof, Robert, Duga, Stefano, Asselta, Rosanna, Pereira, Alexandre C, Romero-Gómez, Manuel, Nafría-Jiménez, Beatriz, Hov, Johannes R, Migeotte, Isabelle, Renieri, Alessandra, Planas, Anna M, Ludwig, Kerstin U, Buti, Maria, Rahmouni, Souad, Alarcón-Riquelme, Marta E, Schulte, Eva C, Franke, Andre, Karlsen, Tom H, Valenti, Luca, Zeberg, Hugo, Richards, Brent, Ganna, Andrea, Boada, Mercè, de Rojas, Itziar, Ruiz, Agustín, Sánchez-Juan, Pascual, Real, Luis Miguel, Guillen-Navarro, Encarna, Ayuso, Carmen, González-Neira, Anna, Riancho, José A, Rojas-Martinez, Augusto, Flores, Carlos, Lapunzina, Pablo, Carracedo, Angel, Cruz, Raquel, Diz-de Almeida, Silvia, López de Heredia, Miguel, Quintela, Inés, Ceballos, Francisco C, Pita, Guillermo, Lorenzo-Salazar, José M, González-Montelongo, Rafaela, Gago-Domínguez, Manuela, Sevilla Porras, Marta, Tenorio Castaño, Jair Antonio, Nevado, Julian, Aguado, Jose María, Aguilar, Carlos, Aguilera-Albesa, Sergio, Almadana, Virginia, Almoguera, Berta, Alvarez, Nuria, Andreu-Bernabeu, Álvaro, Arana-Arri, Eunate, Arango, Celso, Arranz, María J, Artiga, Maria-Jesus, Baptista-Rosas, Raúl C, Barreda-Sánchez, María, Belhassen-Garcia, Moncef, Bezerra, Joao F, Bezerra, Marcos A C, Boix-Palop, Lucía, Brion, María, Brugada, Ramón, Bustos, Matilde, Calderón, Enrique J, Carbonell, Cristina, Castano, Luis, Castelao, Jose E, Conde-Vicente, Rosa, Cordero-Lorenzana, M Lourdes, Cortes-Sanchez, Jose L, Corton, Marta, Darnaude, M Teresa, De Martino-Rodríguez, Alba, Del Campo-Pérez, Victor, Diaz de Bustamante, Aranzazu, Domínguez-Garrido, Elena, Luchessi, Andre D, Eiros, Rocío, Estigarribia Sanabria, Gladys Mercedes, Carmen Fariñas, María, Fernández-Robelo, Uxía, Fernández-Rodríguez, Amanda, Fernández-Villa, Tania, Gil-Fournier, Belén, Gómez-Arrue, Javier, González Álvarez, Beatriz, Gonzalez Bernaldo de Quirós, Fernan, González-Peñas, Javier, Gutiérrez-Bautista, Juan F, Herrero, María José, Herrero-Gonzalez, Antonio, Jimenez-Sousa, María A, Lattig, María Claudia, Liger Borja, Anabel, Lopez-Rodriguez, Rosario, Mancebo, Esther, Martín-López, Caridad, Martín, Vicente, Martinez-Nieto, Oscar, Martinez-Lopez, Iciar, Martinez-Resendez, Michel F, Martinez-Perez, Angel, Mazzeu, Juliana F, Merayo Macías, Eleuterio, Minguez, Pablo, Moreno Cuerda, Victor, Silbiger, Vivian N, Oliveira, Silviene F, Ortega-Paino, Eva, Parellada, Mara, Paz-Artal, Estela, Santos, Ney P C, Pérez-Matute, Patricia, Perez, Patricia, Pérez-Tomás, M Elena, Perucho, Teresa, Pinsach-Abuin, Mel Lina, Pompa-Mera, Ericka N, Porras-Hurtado, Gloria L, Pujol, Aurora, Ramiro León, Soraya, Resino, Salvador, Fernandes, Marianne R, Rodríguez-Ruiz, Emilio, Rodriguez-Artalejo, Fernando, Rodriguez-Garcia, José A, Ruiz Cabello, Francisco, Ruiz-Hornillos, Javier, Ryan, Pablo, Soria, José Manuel, Souto, Juan Carlos, Tamayo, Eduardo, Tamayo-Velasco, Alvaro, Taracido-Fernandez, Juan Carlos, Teper, Alejandro, Torres-Tobar, Lilian, Urioste, Miguel, Valencia-Ramos, Juan, Yáñez, Zuleima, Zarate, Ruth, Nakanishi, Tomoko, Pigazzini, Sara, Degenhardt, Frauke, Butler-Laporte, Guillaume, Maya-Miles, Douglas, Bujanda, Luis, Bouysran, Youssef, Palom, Adriana, Ellinghaus, David, Martínez-Bueno, Manuel, Rolker, Selina, Amitrano, Sara, Roade, Luisa, Fava, Francesca, Spinner, Christoph D, Prati, Daniele, Bernardo, David, Garcia, Federico, Darcis, Gilles, Fernández-Cadenas, Israel, Holter, Jan Cato, Banales, Jesus M, Frithiof, Robert, Duga, Stefano, Asselta, Rosanna, Pereira, Alexandre C, Romero-Gómez, Manuel, Nafría-Jiménez, Beatriz, Hov, Johannes R, Migeotte, Isabelle, Renieri, Alessandra, Planas, Anna M, Ludwig, Kerstin U, Buti, Maria, Rahmouni, Souad, Alarcón-Riquelme, Marta E, Schulte, Eva C, Franke, Andre, Karlsen, Tom H, Valenti, Luca, Zeberg, Hugo, Richards, Brent, Ganna, Andrea, Boada, Mercè, de Rojas, Itziar, Ruiz, Agustín, Sánchez-Juan, Pascual, Real, Luis Miguel, Guillen-Navarro, Encarna, Ayuso, Carmen, González-Neira, Anna, Riancho, José A, Rojas-Martinez, Augusto, Flores, Carlos, Lapunzina, Pablo, and Carracedo, Angel
Abstract: Here, we describe the results of a genome-wide study conducted in 11 939 coronavirus disease 2019 (COVID-19) positive cases with an extensive clinical information that were recruited from 34 hospitals across Spain (SCOURGE consortium). In sex-disaggregated genome-wide association studies for COVID-19 hospitalization, genome-wide significance (P < 5 × 10−8) was crossed for variants in 3p21.31 and 21q22.11 loci only among males (P = 1.3 × 10−22 and P = 8.1 × 10−12, respectively), and for variants in 9q21.32 near TLE1 only among females (P = 4.4 × 10−8). In a second phase, results were combined with an independent Spanish cohort (1598 COVID-19 cases and 1068 population controls), revealing in the overall analysis two novel risk loci in 9p13.3 and 19q13.12, with fine-mapping prioritized variants functionally associated with AQP3 (P = 2.7 × 10−8) and ARHGAP33 (P = 1.3 × 10−8), respectively. The meta-analysis of both phases with four European studies stratified by sex from the Host Genetics Initiative (HGI) confirmed the association of the 3p21.31 and 21q22.11 loci predominantly in males and replicated a recently reported variant in 11p13 (ELF5, P = 4.1 × 10−8). Six of the COVID-19 HGI discovered loci were replicated and an HGI-based genetic risk score predicted the severity strata in SCOURGE. We also found more SNP-heritability and larger heritability differences by age (<60 or ≥60 years) among males than among females. Parallel genome-wide screening of inbreeding depression in SCOURGE also showed an effect of homozygosity in COVID-19 hospitalization and severity and this effect was stronger among older males. In summary, new candidate genes for COVID-19 severity and evidence supporting genetic disparities among sexes are provided.
Published: 2022
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35. ICA1L Is Associated with Small Vessel Disease : A Proteome-Wide Association Study in Small Vessel Stroke and Intracerebral Haemorrhage

Author: Cullell, Natalia, Gallego-Fabrega, Cristina, Cárcel-Márquez, Jara, Muiño, Elena, Llucià-Carol, Laia, Lledós, Miquel, Martín-Campos, Jesús Maria, Molina, Jessica, Casas, Laura, Almeria, Marta, Fernández-Cadenas, Israel, Krupinski, Jerzy, Cullell, Natalia, Gallego-Fabrega, Cristina, Cárcel-Márquez, Jara, Muiño, Elena, Llucià-Carol, Laia, Lledós, Miquel, Martín-Campos, Jesús Maria, Molina, Jessica, Casas, Laura, Almeria, Marta, Fernández-Cadenas, Israel, and Krupinski, Jerzy
Abstract: Small vessel strokes (SVS) and intracerebral haemorrhages (ICH) are acute outcomes of cerebral small vessel disease (SVD). Genetic studies combining both phenotypes have identified three loci associated with both traits. However, the genetic cis-regulation at the protein level associated with SVD has not been studied before. We performed a proteome-wide association study (PWAS) using FUSION to integrate a genome-wide association study (GWAS) and brain proteomic data to discover the common mechanisms regulating both SVS and ICH. Dorsolateral prefrontal cortex (dPFC) brain proteomes from the ROS/MAP study (N = 376 subjects and 1443 proteins) and the summary statistics for the SVS GWAS from the MEGASTROKE study (N = 237,511) and multi-trait analysis of GWAS (MTAG)-ICH-SVS from Chung et al. (N = 240,269) were selected. We performed PWAS and then a co-localization analysis with COLOC. The significant and nominal results were validated using a replication dPFC proteome (N = 152). The replicated results (q -value < 0.05) were further investigated for the causality relationship using summary data-based Mendelian randomization (SMR). One protein (ICA1L) was significantly associated with SVS (z-score = −4.42 and p -value = 9.6 × 10 −6) and non-lobar ICH (z-score = −4.8 and p -value = 1.58 × 10 −6) in the discovery PWAS, with a high co-localization posterior probability of 4. In the validation PWAS, ICA1L remained significantly associated with both traits. The SMR results for ICA1L indicated a causal association of protein expression levels in the brain with SVS (p -value = 3.66 × 10 −5) and non-lobar ICH (p -value = 1.81 × 10 −5). Our results show that the association of ICA1L with SVS and non-lobar ICH is conditioned by the cis-regulation of its protein levels in the brain.
Published: 2022

36. 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

37. 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

38. 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

39. 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

40. Supplementary files of the article 'Novel genes and sex differences in COVID-19 severity' [Dataset]

Author: Cruz Modino, Raquel de la, Diz-de Almeida, Silvia, López de Heredia, Miguel, Quintela, Inés, Ceballos, Francisco C., Pita, Guillermo, Lorenzo-Salazar, José M., González-Montelongo, Rafaela, Gago-Dominguez, Manuela, Sevilla Porras, Marta, Tenorio Castaño, Jair Antonio, Carbonell, Cristina, Migeotte, Isabelle, Renieri, Alessandra, Aguilera-Albesa, Sergio, Planas, Anna M., Ludwig, Kerstin U., Buti, María, Rahmouni, Souad, Alarcón-Riquelme, Marta E., Schulte, Eva C., Tamayo-Velasco, Álvaro, Franke, Andre, Castaño, Luis, Karlsen, Tom H., Valenti, Luca, Zeberg, Hugo, Almadana Pacheco, Virginia, Richards, Brent, Ganna, Andrea, Boada, Mercè, Rojas, Itziar de, Gil-Fournier, Belén, Ruiz, Agustín, Sánchez-Juan, Pascual, Castelao, Jose E., Real, Luis Miguel, SCOURGE Cohort Group, HOSTAGE Cohort Group, GRA@CE Cohort Group, Almoguera, Berta, Guillen-Navarro, Encarna, Ayuso, Carmen, Gómez-Arrue, Javier, González-Neira, Anna, Riancho, José A., Rojas-Martinez, Augusto, Conde-Vicente, Rosa, Flores, Carlos, Lapunzina, Pablo, Carracedo, Ángel, Álvarez, Nuria, Andreu-Bernabeu, Álvaro, Arana-Arri, Eunate, González Álvarez, Beatriz, Arango, Celso, Arranz, Maria J., Artiga, María Jesús, Baptista-Rosas, Raúl C., Cordero-Lorenzana, M. Lourdes, Barreda-Sánchez, María, Belhassen-García, Moncef, Bezerra, Joao F., Bezerra, Marcos A. C., Boix-Palop, Lucía, Gonzalez Bernaldo de Quirós, Fernán, Briones, María, Brugada, Ramón, Bustos, Matilde, Cortés-Sánchez, José L., Cortón, Marta, Darnaude, M. Teresa, Martino-Rodríguez, Alba de, Tamayo, Eduardo, Campo-Pérez, Víctor de, Diaz de Bustamante, Aranzazu, González-Peñas, Javier, Domínguez-Garrido, Elena, Luchessi, Andre D., Eiros, Rocío, Estigarribia Sanabria, Gladys Mercedes, Fariñas, María del Carmen, Fernández-Robelo, Uxía, Fernández-Rodríguez, Amanda, Fernández-Villa, Tania, Gutiérrez-Bautista, Juan F., Herrero, María José, Herrero-Gonzalez, Antonio, Jiménez-Sousa, María A., Aguado, José María, Lattig, María Claudia, Taracido-Fernandez, Juan Carlos, Liger Borja, Anabel, López-Rodríguez, Rosario, Mancebo, Esther, Martín-López, Caridad, Martín, Vicente, Martínez-Nieto, Oscar, Martinez-López, Icíar, Martinez-Resendez, Michel F., Amitrano, Sara, Martínez-Pérez, Àngel, Mazzeu, Juliana F, Teper, Alejandro, Merayo Macías, Eleuterio, Mínguez, Pablo, Moreno Cuerda, Víctor, Silbiger, Vivian N., Oliveira, Silviene F., Ortega-Paino, Eva, Parellada, Mara, Roade, Luisa, Paz-Artal, Estela, Santos, Ney P. C., Pérez-Matute, Patricia, Torres-Tobar, Lilian, Pérez Ramírez, Patricia, Pérez-Tomás, M. Elena, Perucho, Teresa, Pinsach-Abuin, Mel Lina, Pompa-Mera, Ericka N., Porras-Hurtado, Gloria L., Fava, Francesca, Pujol, Aurora, Ramiro León, Soraya, Resino, Salvador, Fernandes, Marianne R., Urioste, Miguel, Rodríguez-Ruiz, Emilio, Rodríguez-Artalejo, Fernando, Rodríguez-García, José A, Ruiz Cabello, Francisco, Ruiz-Hornillos, Javier, Spinner, Christoph D., Ryan, Pablo, Soria, José Manuel, Souto, Juan Carlos, Valencia-Ramos, Juan, Yáñez, Zuleima, Zarate, Ruth, Nakanishi, Tomoko, Nevado, Julian, Pigazzini, Sara, Degenhardt, Frauke, Prati, Daniele, Butler-Laporte, Guillaume, Maya-Miles, Douglas, Bujanda, Luis, Bouysran, Youssef, Palom, Adriana, Ellinghaus, David, Martínez-Bueno, Manuel, Rolker, Selina, Bernardo, David, García, Federico, Darcis, Gilles, Fernández-Cadenas, Israel, Calderón, Enrique J., Holter, Jan Cato, Aguilar, Carlos, Banales, Jesús M., Frithiof, Robert, Duga, Stefano, Asselta, Rosanna, Pereira, Alexandre C., Romero-Gómez, Manuel, Nafría-Jiménez, Beatriz, Hov, Johannes R., Cruz Modino, Raquel de la, Diz-de Almeida, Silvia, López de Heredia, Miguel, Quintela, Inés, Ceballos, Francisco C., Pita, Guillermo, Lorenzo-Salazar, José M., González-Montelongo, Rafaela, Gago-Dominguez, Manuela, Sevilla Porras, Marta, Tenorio Castaño, Jair Antonio, Carbonell, Cristina, Migeotte, Isabelle, Renieri, Alessandra, Aguilera-Albesa, Sergio, Planas, Anna M., Ludwig, Kerstin U., Buti, María, Rahmouni, Souad, Alarcón-Riquelme, Marta E., Schulte, Eva C., Tamayo-Velasco, Álvaro, Franke, Andre, Castaño, Luis, Karlsen, Tom H., Valenti, Luca, Zeberg, Hugo, Almadana Pacheco, Virginia, Richards, Brent, Ganna, Andrea, Boada, Mercè, Rojas, Itziar de, Gil-Fournier, Belén, Ruiz, Agustín, Sánchez-Juan, Pascual, Castelao, Jose E., Real, Luis Miguel, SCOURGE Cohort Group, HOSTAGE Cohort Group, GRA@CE Cohort Group, Almoguera, Berta, Guillen-Navarro, Encarna, Ayuso, Carmen, Gómez-Arrue, Javier, González-Neira, Anna, Riancho, José A., Rojas-Martinez, Augusto, Conde-Vicente, Rosa, Flores, Carlos, Lapunzina, Pablo, Carracedo, Ángel, Álvarez, Nuria, Andreu-Bernabeu, Álvaro, Arana-Arri, Eunate, González Álvarez, Beatriz, Arango, Celso, Arranz, Maria J., Artiga, María Jesús, Baptista-Rosas, Raúl C., Cordero-Lorenzana, M. Lourdes, Barreda-Sánchez, María, Belhassen-García, Moncef, Bezerra, Joao F., Bezerra, Marcos A. C., Boix-Palop, Lucía, Gonzalez Bernaldo de Quirós, Fernán, Briones, María, Brugada, Ramón, Bustos, Matilde, Cortés-Sánchez, José L., Cortón, Marta, Darnaude, M. Teresa, Martino-Rodríguez, Alba de, Tamayo, Eduardo, Campo-Pérez, Víctor de, Diaz de Bustamante, Aranzazu, González-Peñas, Javier, Domínguez-Garrido, Elena, Luchessi, Andre D., Eiros, Rocío, Estigarribia Sanabria, Gladys Mercedes, Fariñas, María del Carmen, Fernández-Robelo, Uxía, Fernández-Rodríguez, Amanda, Fernández-Villa, Tania, Gutiérrez-Bautista, Juan F., Herrero, María José, Herrero-Gonzalez, Antonio, Jiménez-Sousa, María A., Aguado, José María, Lattig, María Claudia, Taracido-Fernandez, Juan Carlos, Liger Borja, Anabel, López-Rodríguez, Rosario, Mancebo, Esther, Martín-López, Caridad, Martín, Vicente, Martínez-Nieto, Oscar, Martinez-López, Icíar, Martinez-Resendez, Michel F., Amitrano, Sara, Martínez-Pérez, Àngel, Mazzeu, Juliana F, Teper, Alejandro, Merayo Macías, Eleuterio, Mínguez, Pablo, Moreno Cuerda, Víctor, Silbiger, Vivian N., Oliveira, Silviene F., Ortega-Paino, Eva, Parellada, Mara, Roade, Luisa, Paz-Artal, Estela, Santos, Ney P. C., Pérez-Matute, Patricia, Torres-Tobar, Lilian, Pérez Ramírez, Patricia, Pérez-Tomás, M. Elena, Perucho, Teresa, Pinsach-Abuin, Mel Lina, Pompa-Mera, Ericka N., Porras-Hurtado, Gloria L., Fava, Francesca, Pujol, Aurora, Ramiro León, Soraya, Resino, Salvador, Fernandes, Marianne R., Urioste, Miguel, Rodríguez-Ruiz, Emilio, Rodríguez-Artalejo, Fernando, Rodríguez-García, José A, Ruiz Cabello, Francisco, Ruiz-Hornillos, Javier, Spinner, Christoph D., Ryan, Pablo, Soria, José Manuel, Souto, Juan Carlos, Valencia-Ramos, Juan, Yáñez, Zuleima, Zarate, Ruth, Nakanishi, Tomoko, Nevado, Julian, Pigazzini, Sara, Degenhardt, Frauke, Prati, Daniele, Butler-Laporte, Guillaume, Maya-Miles, Douglas, Bujanda, Luis, Bouysran, Youssef, Palom, Adriana, Ellinghaus, David, Martínez-Bueno, Manuel, Rolker, Selina, Bernardo, David, García, Federico, Darcis, Gilles, Fernández-Cadenas, Israel, Calderón, Enrique J., Holter, Jan Cato, Aguilar, Carlos, Banales, Jesús M., Frithiof, Robert, Duga, Stefano, Asselta, Rosanna, Pereira, Alexandre C., Romero-Gómez, Manuel, Nafría-Jiménez, Beatriz, and Hov, Johannes R.
Published: 2022

41. 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

42. 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

43. Genome-Wide Studies in Ischaemic Stroke: Are Genetics Only Useful for Finding Genes?

Author: 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.
Published: 2022

44. Novel genes and sex differences in COVID-19 severity

Author: Instituto de Salud Carlos III, European Commission, Fundación Amancio Ortega, Banco Santander, Estrella de Levante, Colabora Mujer, Fundación Canaria Instituto de Investigación Sanitaria de Canarias, Cruz Modino, Raquel de la, Diz-de Almeida, Silvia, López de Heredia, Miguel, Quintela, Inés, Ceballos, Francisco C., Pita, Guillermo, Lorenzo-Salazar, José M., González-Montelongo, Rafaela, Gago-Dominguez, Manuela, Sevilla Porras, Marta, Tenorio Castaño, Jair Antonio, Carbonell, Cristina, Migeotte, Isabelle, Renieri, Alessandra, Aguilera-Albesa, Sergio, Planas, Anna M., Ludwig, Kerstin U., Buti, María, Rahmouni, Souad, Alarcón-Riquelme, Marta E., Schulte, Eva C., Tamayo-Velasco, Álvaro, Franke, Andre, Castaño, Luis, Karlsen, Tom H., Valenti, Luca, Zeberg, Hugo, Almadana Pacheco, Virginia, Richards, Brent, Ganna, Andrea, Boada, Mercè, Rojas, Itziar de, Gil-Fournier, Belén, Ruiz, Agustín, Sánchez-Juan, Pascual, Castelao, Jose E., Real, Luis Miguel, SCOURGE Cohort Group, HOSTAGE Cohort Group, GRA@CE Cohort Group, Almoguera, Berta, Guillen-Navarro, Encarna, Ayuso, Carmen, Gómez-Arrue, Javier, González-Neira, Anna, Riancho, José A., Rojas-Martinez, Augusto, Conde-Vicente, Rosa, Flores, Carlos, Lapunzina, Pablo, Carracedo, Ángel, Álvarez, Nuria, Andreu-Bernabeu, Álvaro, Arana-Arri, Eunate, González Álvarez, Beatriz, Arango, Celso, Arranz, Maria J., Artiga, María Jesús, Baptista-Rosas, Raúl C., Cordero-Lorenzana, M. Lourdes, Barreda-Sánchez, María, Belhassen-García, Moncef, Bezerra, Joao F., Bezerra, Marcos A. C., Boix-Palop, Lucía, Gonzalez Bernaldo de Quirós, Fernán, Briones, María, Brugada, Ramón, Bustos, Matilde, Cortés-Sánchez, José L., Cortón, Marta, Darnaude, M. Teresa, Martino-Rodríguez, Alba de, Tamayo, Eduardo, Campo-Pérez, Víctor de, Diaz de Bustamante, Aranzazu, González-Peñas, Javier, Domínguez-Garrido, Elena, Luchessi, Andre D., Eiros, Rocío, Estigarribia Sanabria, Gladys Mercedes, Fariñas, María del Carmen, Fernández-Robelo, Uxía, Fernández-Rodríguez, Amanda, Fernández-Villa, Tania, Gutiérrez-Bautista, Juan F., Herrero, María José, Herrero-Gonzalez, Antonio, Jiménez-Sousa, María A., Aguado, José María, Lattig, María Claudia, Taracido-Fernandez, Juan Carlos, Liger Borja, Anabel, López-Rodríguez, Rosario, Mancebo, Esther, Martín-López, Caridad, Martín, Vicente, Martínez-Nieto, Oscar, Martinez-López, Icíar, Martinez-Resendez, Michel F., Amitrano, Sara, Martínez-Pérez, Àngel, Mazzeu, Juliana F, Teper, Alejandro, Merayo Macías, Eleuterio, Mínguez, Pablo, Moreno Cuerda, Víctor, Silbiger, Vivian N., Oliveira, Silviene F., Ortega-Paino, Eva, Parellada, Mara, Roade, Luisa, Paz-Artal, Estela, Santos, Ney P. C., Pérez-Matute, Patricia, Torres-Tobar, Lilian, Pérez Ramírez, Patricia, Pérez-Tomás, M. Elena, Perucho, Teresa, Pinsach-Abuin, Mel Lina, Pompa-Mera, Ericka N., Porras-Hurtado, Gloria L., Fava, Francesca, Pujol, Aurora, Ramiro León, Soraya, Resino, Salvador, Fernandes, Marianne R., Urioste, Miguel, Rodríguez-Ruiz, Emilio, Rodríguez-Artalejo, Fernando, Rodríguez-García, José A, Ruiz Cabello, Francisco, Ruiz-Hornillos, Javier, Spinner, Christoph D., Ryan, Pablo, Soria, José Manuel, Souto, Juan Carlos, Valencia-Ramos, Juan, Yáñez, Zuleima, Zarate, Ruth, Nakanishi, Tomoko, Nevado, Julian, Pigazzini, Sara, Degenhardt, Frauke, Prati, Daniele, Butler-Laporte, Guillaume, Maya-Miles, Douglas, Bujanda, Luis, Bouysran, Youssef, Palom, Adriana, Ellinghaus, David, Martínez-Bueno, Manuel, Rolker, Selina, Bernardo, David, García, Federico, Darcis, Gilles, Fernández-Cadenas, Israel, Calderón, Enrique J., Holter, Jan Cato, Aguilar, Carlos, Banales, Jesús M., Frithiof, Robert, Duga, Stefano, Asselta, Rosanna, Pereira, Alexandre C., Romero-Gómez, Manuel, Nafría-Jiménez, Beatriz, Hov, Johannes R., Instituto de Salud Carlos III, European Commission, Fundación Amancio Ortega, Banco Santander, Estrella de Levante, Colabora Mujer, Fundación Canaria Instituto de Investigación Sanitaria de Canarias, Cruz Modino, Raquel de la, Diz-de Almeida, Silvia, López de Heredia, Miguel, Quintela, Inés, Ceballos, Francisco C., Pita, Guillermo, Lorenzo-Salazar, José M., González-Montelongo, Rafaela, Gago-Dominguez, Manuela, Sevilla Porras, Marta, Tenorio Castaño, Jair Antonio, Carbonell, Cristina, Migeotte, Isabelle, Renieri, Alessandra, Aguilera-Albesa, Sergio, Planas, Anna M., Ludwig, Kerstin U., Buti, María, Rahmouni, Souad, Alarcón-Riquelme, Marta E., Schulte, Eva C., Tamayo-Velasco, Álvaro, Franke, Andre, Castaño, Luis, Karlsen, Tom H., Valenti, Luca, Zeberg, Hugo, Almadana Pacheco, Virginia, Richards, Brent, Ganna, Andrea, Boada, Mercè, Rojas, Itziar de, Gil-Fournier, Belén, Ruiz, Agustín, Sánchez-Juan, Pascual, Castelao, Jose E., Real, Luis Miguel, SCOURGE Cohort Group, HOSTAGE Cohort Group, GRA@CE Cohort Group, Almoguera, Berta, Guillen-Navarro, Encarna, Ayuso, Carmen, Gómez-Arrue, Javier, González-Neira, Anna, Riancho, José A., Rojas-Martinez, Augusto, Conde-Vicente, Rosa, Flores, Carlos, Lapunzina, Pablo, Carracedo, Ángel, Álvarez, Nuria, Andreu-Bernabeu, Álvaro, Arana-Arri, Eunate, González Álvarez, Beatriz, Arango, Celso, Arranz, Maria J., Artiga, María Jesús, Baptista-Rosas, Raúl C., Cordero-Lorenzana, M. Lourdes, Barreda-Sánchez, María, Belhassen-García, Moncef, Bezerra, Joao F., Bezerra, Marcos A. C., Boix-Palop, Lucía, Gonzalez Bernaldo de Quirós, Fernán, Briones, María, Brugada, Ramón, Bustos, Matilde, Cortés-Sánchez, José L., Cortón, Marta, Darnaude, M. Teresa, Martino-Rodríguez, Alba de, Tamayo, Eduardo, Campo-Pérez, Víctor de, Diaz de Bustamante, Aranzazu, González-Peñas, Javier, Domínguez-Garrido, Elena, Luchessi, Andre D., Eiros, Rocío, Estigarribia Sanabria, Gladys Mercedes, Fariñas, María del Carmen, Fernández-Robelo, Uxía, Fernández-Rodríguez, Amanda, Fernández-Villa, Tania, Gutiérrez-Bautista, Juan F., Herrero, María José, Herrero-Gonzalez, Antonio, Jiménez-Sousa, María A., Aguado, José María, Lattig, María Claudia, Taracido-Fernandez, Juan Carlos, Liger Borja, Anabel, López-Rodríguez, Rosario, Mancebo, Esther, Martín-López, Caridad, Martín, Vicente, Martínez-Nieto, Oscar, Martinez-López, Icíar, Martinez-Resendez, Michel F., Amitrano, Sara, Martínez-Pérez, Àngel, Mazzeu, Juliana F, Teper, Alejandro, Merayo Macías, Eleuterio, Mínguez, Pablo, Moreno Cuerda, Víctor, Silbiger, Vivian N., Oliveira, Silviene F., Ortega-Paino, Eva, Parellada, Mara, Roade, Luisa, Paz-Artal, Estela, Santos, Ney P. C., Pérez-Matute, Patricia, Torres-Tobar, Lilian, Pérez Ramírez, Patricia, Pérez-Tomás, M. Elena, Perucho, Teresa, Pinsach-Abuin, Mel Lina, Pompa-Mera, Ericka N., Porras-Hurtado, Gloria L., Fava, Francesca, Pujol, Aurora, Ramiro León, Soraya, Resino, Salvador, Fernandes, Marianne R., Urioste, Miguel, Rodríguez-Ruiz, Emilio, Rodríguez-Artalejo, Fernando, Rodríguez-García, José A, Ruiz Cabello, Francisco, Ruiz-Hornillos, Javier, Spinner, Christoph D., Ryan, Pablo, Soria, José Manuel, Souto, Juan Carlos, Valencia-Ramos, Juan, Yáñez, Zuleima, Zarate, Ruth, Nakanishi, Tomoko, Nevado, Julian, Pigazzini, Sara, Degenhardt, Frauke, Prati, Daniele, Butler-Laporte, Guillaume, Maya-Miles, Douglas, Bujanda, Luis, Bouysran, Youssef, Palom, Adriana, Ellinghaus, David, Martínez-Bueno, Manuel, Rolker, Selina, Bernardo, David, García, Federico, Darcis, Gilles, Fernández-Cadenas, Israel, Calderón, Enrique J., Holter, Jan Cato, Aguilar, Carlos, Banales, Jesús M., Frithiof, Robert, Duga, Stefano, Asselta, Rosanna, Pereira, Alexandre C., Romero-Gómez, Manuel, Nafría-Jiménez, Beatriz, and Hov, Johannes R.
Abstract: Here, we describe the results of a genome-wide study conducted in 11 939 coronavirus disease 2019 (COVID-19) positive cases with an extensive clinical information that were recruited from 34 hospitals across Spain (SCOURGE consortium). In sex-disaggregated genome-wide association studies for COVID-19 hospitalization, genome-wide significance (P < 5 × 10-8) was crossed for variants in 3p21.31 and 21q22.11 loci only among males (P = 1.3 × 10-22 and P = 8.1 × 10-12, respectively), and for variants in 9q21.32 near TLE1 only among females (P = 4.4 × 10-8). In a second phase, results were combined with an independent Spanish cohort (1598 COVID-19 cases and 1068 population controls), revealing in the overall analysis two novel risk loci in 9p13.3 and 19q13.12, with fine-mapping prioritized variants functionally associated with AQP3 (P = 2.7 × 10-8) and ARHGAP33 (P = 1.3 × 10-8), respectively. The meta-analysis of both phases with four European studies stratified by sex from the Host Genetics Initiative (HGI) confirmed the association of the 3p21.31 and 21q22.11 loci predominantly in males and replicated a recently reported variant in 11p13 (ELF5, P = 4.1 × 10-8). Six of the COVID-19 HGI discovered loci were replicated and an HGI-based genetic risk score predicted the severity strata in SCOURGE. We also found more SNP-heritability and larger heritability differences by age (<60 or ≥60 years) among males than among females. Parallel genome-wide screening of inbreeding depression in SCOURGE also showed an effect of homozygosity in COVID-19 hospitalization and severity and this effect was stronger among older males. In summary, new candidate genes for COVID-19 severity and evidence supporting genetic disparities among sexes are provided.
Published: 2022

45. 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

46. GRECOS Project (Genotyping Recurrence Risk of Stroke): The Use of Genetics to Predict the Vascular Recurrence After Stroke

Author: Fernández-Cadenas, Israel, Mendióroz, Maite, Giralt, Dolors, Nafria, Cristina, Garcia, Elena, Carrera, Caty, Gallego-Fabrega, Cristina, Domingues-Montanari, Sophie, Delgado, Pilar, Ribó, Marc, Castellanos, Mar, Martínez, Sergi, Freijo, Marimar, Jiménez-Conde, Jordi, Rubiera, Marta, Alvarez-Sabín, José, Molina, Carlos A., Font, Maria Angels, Grau Olivares, Marta, Palomeras, Ernest, Perez de la Ossa, Natalia, Martinez-Zabaleta, Maite, Masjuan, Jaime, Moniche, Francisco, Canovas, David, Piñana, Carlos, Purroy, Francisco, Cocho, Dolores, Navas, Inma, Tejero, Carlos, Aymerich, Nuria, Cullell, Natalia, Muiño, Elena, Serena, Joaquín, Rubio, Francisco, Davalos, Antoni, Roquer, Jaume, Arenillas, Juan Francisco, Martí-Fábregas, Joan, Keene, Keith, Chen, Wei-Min, Worrall, Bradford, Sale, Michele, Arboix, Adrià, Krupinski, Jerzy, and Montaner, Joan
Published: 2017
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47. Genetic risk factors for ischaemic stroke and its subtypes (the METASTROKE Collaboration): a meta-analysis of genome-wide association studies

Author: Traylor, Matthew, Farrall, Martin, Holliday, Elizabeth G, Sudlow, Cathie, Hopewell, Jemma C, Cheng, Yu-Ching, Fornage, Myriam, Ikram, M Arfan, Malik, Rainer, Bevan, Steve, Thorsteinsdottir, Unnur, Nalls, Mike A, Longstreth, WT, Wiggins, Kerri L, Yadav, Sunaina, Parati, Eugenio A, DeStefano, Anita L, Worrall, Bradford B, Kittner, Steven J, Khan, Muhammad Saleem, Reiner, Alex P, Helgadottir, Anna, Achterberg, Sefanja, Fernandez-Cadenas, Israel, Abboud, Sherine, Schmidt, Reinhold, Walters, Matthew, Chen, Wei-Min, Ringelstein, E Bernd, O'Donnell, Martin, Ho, Weang Kee, Pera, Joanna, Lemmens, Robin, Norrving, Bo, Higgins, Peter, Benn, Marianne, Sale, Michele, Kuhlenbäumer, Gregor, Doney, Alexander S F, Vicente, Astrid M, Delavaran, Hossein, Algra, Ale, Davies, Gail, Oliveira, Sofia A, Palmer, Colin N A, Deary, Ian, Schmidt, Helena, Pandolfo, Massimo, Montaner, Joan, Carty, Cara, de Bakker, Paul I W, Kostulas, Konstantinos, Ferro, Jose M, van Zuydam, Natalie R, Valdimarsson, Einar, Nordestgaard, Børge G, Lindgren, Arne, Thijs, Vincent, Slowik, Agnieszka, Saleheen, Danish, Paré, Guillaume, Berger, Klaus, Thorleifsson, Gudmar, Hofman, Albert, Mosley, Thomas H, Mitchell, Braxton D, Furie, Karen, Clarke, Robert, Levi, Christopher, Seshadri, Sudha, Gschwendtner, Andreas, Boncoraglio, Giorgio B, Sharma, Pankaj, Bis, Joshua C, Gretarsdottir, Solveig, Psaty, Bruce M, Rothwell, Peter M, Rosand, Jonathan, Meschia, James F, Stefansson, Kari, Dichgans, Martin, and Markus, Hugh S
Published: 2012
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48. Differentiating ischemic from hemorrhagic stroke using plasma biomarkers: The S100B/RAGE pathway

Author: Montaner, Joan, Mendioroz, Maite, Delgado, Pilar, García-Berrocoso, Teresa, Giralt, Dolors, Merino, Cristina, Ribó, Marc, Rosell, Anna, Penalba, Anna, Fernández-Cadenas, Israel, Romero, Francisco, Molina, Carlos, Alvarez-Sabín, Jose, and Hernández-Guillamon, Mar
Published: 2012
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49. Altered methylation pattern in EXOC4 is associated with stroke outcome: an Epigenome- Wide Association Study

Author: Cullell, Natalia, primary, Soriano-Tárraga, Carolina, additional, Gallego-Fábrega, Cristina, additional, Cárcel-Márquez, Jara, additional, Muiño, Elena, additional, Llucià-Carol, Laia, additional, Lledós, Miquel, additional, Esteller, Manel, additional, Moura, Manuel Castro, additional, Montaner, Joan, additional, Rosell, Anna, additional, Delgado, Pilar, additional, Martí-Fábregas, Joan, additional, Krupinski, Jerzy, additional, Roquer, Jaume, additional, Jiménez-Conde, Jordi, additional, and Fernández-Cadenas, Israel, additional
Published: 2022
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50. ICA1L Is Associated with Small Vessel Disease: A Proteome-Wide Association Study in Small Vessel Stroke and Intracerebral Haemorrhage

Author: Cullell, Natalia, primary, Gallego-Fábrega, Cristina, additional, Cárcel-Márquez, Jara, additional, Muiño, Elena, additional, Llucià-Carol, Laia, additional, Lledós, Miquel, additional, Martín-Campos, Jesús M., additional, Molina, Jessica, additional, Casas, Laura, additional, Almeria, Marta, additional, Fernández-Cadenas, Israel, additional, and Krupinski, Jerzy, additional
Published: 2022
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