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33 results on '"Rannikmae, Kristiina"'

1. Fine-mapping of retinal vascular complexity loci identifies Notch regulation as a shared mechanism with myocardial infarction outcomes

Author

Villaplana-Velasco, Ana, Pigeyre, Marie, Engelmann, Justin, Rawlik, Konrad, Canela-Xandri, Oriol, Tochel, Claire, Lona-Durazo, Frida, Mookiah, Muthu Rama Krishnan, Doney, Alex, Parra, Esteban J., Trucco, Emanuele, MacGillivray, Tom, Rannikmae, Kristiina, Tenesa, Albert, Pairo-Castineira, Erola, and Bernabeu, Miguel O.

Published
2023
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2. Contribution of Common Genetic Variants to Risk of Early Onset Ischemic Stroke

Author

Jaworek, Thomas, Xu, Huichun, Gaynor, Brady J, Cole, John W., Rannikmae, Kristiina, Stanne, Tara M, Tomppo, Liisa, Abedi, Vida, Amouyel, Philippe, Armstrong, Nicole D, Attia, John, Bell, Steven, Benavente, Oscar R, Boncoraglio, Giorgio B, Butterworth, Adam, Carcel-Marquez, Jara, Chen, Zhengming, Chong, Michael, Cruchaga, Carlos, Cushman, Mary, Danesh, John, Debette, Stephanie, Duggan, David J, Durda, Jon Peter, Engstrom, Gunnar, Enzinger, Chris, Faul, Jessica D, Fecteau, Natalie S, Fernandez-Cadenas, Israel, Gieger, Christian, Giese, Anne-Katrin, Grewal, Raji P, Grittner, Ulrike, Havulinna, Aki S, Heitsch, Laura, Hochberg, Marc C, Holliday, Elizabeth, Hu, Jie, Ilinca, Andreea, Irvin, Marguerite R, Jackson, Rebecca D, Jacob, Mina A., Janssen, Raquel Rabionet, Jimenez-Conde, Jordi, Johnson, Julie A, Kamatani, Yoichiro, Kardia, Sharon L, Koido, Masaru, Kubo, Michiaki, Lange, Leslie, Lee, Jin-Moo, Lemmens, Robin, Levi, Christopher R, Li, Jiang, Li, Liming, Lin, Kuang, Lopez, Haley, Luke, Sothear, Maguire, Jane, McArdle, Patrick F, McDonough, Caitrin W., Meschia, James F, Metso, Tiina, Muller-Nurasyid, Martina, OʼConnor, Timothy D, OʼDonnell, Martin, Peddareddygari, Leema R, Pera, Joanna, Perry, James A, Peters, Annette, Putaala, Jukka, Ray, Debashree, Rexrode, Kathryn, Ribases, Marta, Rosand, Jonathan, Rothwell, Peter M, Rundek, Tatjana, Ryan, Kathleen A, Sacco, Ralph L., Salomaa, Veikko, Sanchez-Mora, Cristina, Schmidt, Reinhold, Sharma, Pankaj, Slowik, Agnieszka, Smith, Jennifer A, Smith, Nicholas L, Wassertheil-Smoller, Sylvia, Soederholm, Martin, Stine, O. C, Strbian, Daniel, Sudlow, Cathie L, Tatlisumak, Turgut, Terao, Chikashi, Thijs, Vincent, Torres-Aguila, Nuria P, Tregouet, David-Alexandre, Tuladhar, Anil M., Veldink, Jan H, Walters, Robin G, Weir, David R, Woo, Daniel, Worrall, Bradford B, Hong, Charles C, Ross, Owen, Zand, Ramin, Leeuw, Frank-Erik de, Lindgren, Arne G, Pare, Guillaume, Anderson, Christopher D., Markus, Hugh S, Jern, Christina, Malik, Rainer, Dichgans, Martin, Mitchell, Braxton D, and Kittner, Steven J

Published
2022
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5. Genetic and lifestyle risk factors for MRI-defined brain infarcts in a population-based setting

Author

Chauhan, Ganesh, Adams, Hieab H.H., Satizabal, Claudia L., Bis, Joshua C., Teumer, Alexander, Sargurupremraj, Muralidharan, Hofer, Edith, Trompet, Stella, Hilal, Saima, Smith, Albert Vernon, Jian, Xueqiu, Malik, Rainer, Traylor, Matthew, Pulit, Sara L., Amouyel, Philippe, Mazoyer, Bernard, Zhu, Yi-Cheng, Kaffashian, Sara, Schilling, Sabrina, Beecham, Gary W., Montine, Thomas J., Schellenberg, Gerard D., Kjartansson, Olafur, Guðnason, Vilmundur, Knopman, David S., Griswold, Michael E., Windham, B. Gwen, Gottesman, Rebecca F., Mosley, Thomas H., Schmidt, Reinhold, Saba, Yasaman, Schmidt, Helena, Takeuchi, Fumihiko, Yamaguchi, Shuhei, Nabika, Toru, Kato, Norihiro, Rajan, Kumar B., Aggarwal, Neelum T., De Jager, Philip L., Evans, Denis A., Psaty, Bruce M., Rotter, Jerome I., Rice, Kenneth, Lopez, Oscar L., Liao, Jiemin, Chen, Christopher, Cheng, Ching-Yu, Wong, Tien Y., Ikram, Mohammad K., van der Lee, Sven J., Amin, Najaf, Chouraki, Vincent, DeStefano, Anita L., Aparicio, Hugo J., Romero, Jose R., Maillard, Pauline, DeCarli, Charles, Wardlaw, Joanna M., Hernández, Maria del C. Valdés, Luciano, Michelle, Liewald, David, Deary, Ian J., Starr, John M., Bastin, Mark E., Muñoz Maniega, Susana, Slagboom, P. Eline, Beekman, Marian, Deelen, Joris, Uh, Hae-Won, Lemmens, Robin, Brodaty, Henry, Wright, Margaret J., Ames, David, Boncoraglio, Giorgio B., Hopewell, Jemma C., Beecham, Ashley H., Blanton, Susan H., Wright, Clinton B., Sacco, Ralph L., Wen, Wei, Thalamuthu, Anbupalam, Armstrong, Nicola J., Chong, Elizabeth, Schofield, Peter R., Kwok, John B., van der Grond, Jeroen, Stott, David J., Ford, Ian, Jukema, J. Wouter, Vernooij, Meike W., Hofman, Albert, Uitterlinden, André G., van der Lugt, Aad, Wittfeld, Katharina, Grabe, Hans J., Hosten, Norbert, von Sarnowski, Bettina, Völker, Uwe, Levi, Christopher, Jimenez-Conde, Jordi, Sharma, Pankaj, Sudlow, Cathie L.M., Rosand, Jonathan, Woo, Daniel, Cole, John W., Meschia, James F., Slowik, Agnieszka, Thijs, Vincent, Lindgren, Arne, Melander, Olle, Grewal, Raji P., Rundek, Tatjana, Rexrode, Kathy, Rothwell, Peter M., Arnett, Donna K., Jern, Christina, Johnson, Julie A., Benavente, Oscar R., Wasssertheil-Smoller, Sylvia, Lee, Jin-Moo, Wong, Quenna, Mitchell, Braxton D., Rich, Stephen S., McArdle, Patrick F., Geerlings, Mirjam I., van der Graaf, Yolanda, de Bakker, Paul I.W., Asselbergs, Folkert W., Srikanth, Velandai, Thomson, Russell, McWhirter, Rebekah, Moran, Chris, Callisaya, Michele, Phan, Thanh, Rutten-Jacobs, Loes C.A., Bevan, Steve, Tzourio, Christophe, Mather, Karen A., Sachdev, Perminder S., van Duijn, Cornelia M., Worrall, Bradford B., Dichgans, Martin, Kittner, Steven J., Markus, Hugh S., Ikram, Mohammad A., Fornage, Myriam, Launer, Lenore J., Seshadri, Sudha, Longstreth, W.T., Jr, Debette, Stéphanie, Almgren, Peter, Anderson, Christopher D., Arnett, Donna K., Attia, John, Ay, Hakan, Benavente, Oscar R., Bevan, Steve, Brown, Robert D., Bustamante, Mariana, Cheng, Yu-Ching, Cole, John W., Cotlarciuc, Ioana, Cruchaga, Carlos, de Bakker, Paul IW., Delavaran, Hossein, Dichgans, Martin, Engström, Gunnar, Fornage, Myriam, Grewal, Raji P., Heitsch, Laura, Holliday, Elizabeth, Ibanez, Laure, Ilinca, Andreea, Irvin, Marguerite R., Jackson, Rebecca D., Jern, Christina, Jimenez-Conde, Jordi, Johnson, Julie A., Jood, Katarina, Kissela, Brett M., Kittner, Steven J., Kleindorfer, Dawn O., Labovitz, Daniel, Laurie, Cathy C., Lee, Jin-Moo, Lemmens, Robin, Levi, Christopher, Li, Linxin, Lindgren, Arne G., Maguire, Jane, Markus, Hugh S., McArdle, Patrick F., Melander, Olle, Meschia, James F., Mitchell, Braxton D., Müller-Nurasyid, Martina, Norrving, Bo, Peddareddygari, Leema Reddy, Pera, Joanna, Pulit, Sara L., Rexrode, Kathryn, Ribasés, Marta, Roquer, Jaume, Rost, Natalia S., Rothwell, Peter M., Rundek, Tatjana, Sacco, Ralph L., Schmidt, Reinhold, Sharma, Pankaj, Slowik, Agnieszka, Soriano-Tárraga, Carolina, Stanne, Tara, Stauch, Konstantin, Stine, O C., Sudlow, Cathie LM., Thijs, Vincent N.S., Wasssertheil-Smoller, Sylvia, Weir, David, Williams, Stephen R., Wong, Quenna, Woo, Daniel, Worrall, Bradford B., Xu, Huichun, Seshadri, Sudha, Hyacinth, Hyacinth I, Marini, Sandro, Nyquist, Paul, Lewis, Cathryn, Hansen, Bjorn, Norrving, Bo, Rosand, Jonathan, Biffi, Alessandro, Kourkoulis, Christina, Anderson, Chris, Giese, Anne-Katrin, Sacco, Ralph, Sharma, Pankaj, Chung, Jong-Won, Kim, Gyeong-Moon, Lubitz, Steven, Bourcier, Romain, Howson, Joanna, Granata, Alessandra, Drazyk, Anna, Markus, Hugh, Wardlaw, Joanna, Mitchell, Braxton, Cole, John, Hopewell, Jemma, Walters, Robin, Turnbull, Iain, Worrall, Bradford, Bis, Josh, Reiner, Alex, Dhar, Raj, Heitsch, Laura, Lee, Jin-Moo, Prasad, Kameshwar, Sarnowski, Chloé, Aparicio, Hugo Javier, Yang, Qiong, Chasman, Daniel, Rexrode, Kathryn, Phuah, Chia-Ling, Liu, Guiyou, Elkind, Mitchell, Lange, Leslie, Rost, Natalia, James, Michael, Stewart, Jill, Vojinovic, Dina, Thijs, Vincent, Parati, Eugenio, Boncoraglio, Giorgio, Zand, Ramin, Bijlenga, Philippe, Selim, Magdy, Grond-Ginsbach, Caspar, Strbian, Daniel, Tomppo, Liisa, Sallinen, Hanne, Pfeiffer, Dorothea, Torres, Nuria, Barboza, Miguel, Laarman, Melanie, Carriero, Roberta, Holliday, Elizabeth, Jimenez-Conde, Jordi, Soriano, Carolina, Gill, Dipender, Debette, Stephanie, Mishra, Aniket, Wu, Jer-Yuarn, Ko, Tai-Ming, Bione, Silvia, Jood, Katarina, Tatlisumak, Turgut, Holmegaard, Lukas, Yue, Suo, bersano, Anna, Pera, Joanna, Slowik, Agnieszka, Levi, Christopher, Schlicht, Kristina, Lemmens, Robin, Ninomiya, Toshiharu, Oberstein, Saskia Lesnik, Lee, Tsong-Hai, Malik, Rainer, Dichgans, Martin, Lindgren, Arne, Wasselius, Johan, Drake, Mattias, Melander, Olle, Stenman, Martin, Ilinca, Andreea, Crawford, Katherine, Lena, Umme, Mateen, Farrah, Ay, Hakan, Wu, Ona, Schirmer, Markus, Cramer, Steve, Golland, Polina, Brown, Robert, Meschia, James, Ross, Owen A., Pare, Guillaume, Chong, Mike, Rundek, Tatjana, Gwinn, Katrina, Chen, Christopher, Koenig, Jim, Giralt, Eva, Saleheen, Danish, de Leeuw, Frank-Erik, Klijn, Karin, Kamatani, Yoichiro, Kubo, Michiaki, Okada, Yukinori, Pedersen, Annie, Olsson, Maja, Martín, Juan José, Xu, Huichun, Tan, Eng King, Frid, Petrea, Lee, Chaeyoung, Tregouet, David, Leung, Thomas, Choy, Richard, Jern, Christina, Loo, Keat Wei, Rinkel, Gabriel, Franca, Paulo, Cendes, Iscia, Carrera, Caty, Fernandez-Cadenas, Israel, Montaner, Joan, Kim, Helen, Owolabi, Mayowa, Sofat, Reecha, Bakker, Mark, Ruigrok, Ynte, Hauer, Allard, Pulit, Sara L., van der Laan, Sander W., Irvin, Ryan, Sargurupremraj, Murali, Pezzini, Alessandro, Abd-Allah, Foad, Liebeskind, David, Traylor, Matthew, Tan, Rhea, Danesh, John, Rutten-Jacobs, Loes, Donatti, Amanda, Avelar, Wagner, Broderick, Joseph, Woo, Daniel, Sudlow, Cathie, Rannikmae, Kristiina, McDonough, Caitrin Wheeler, van Agtmael, Tom, Walters, Matthew, Söderholm, Martin, Lorentzen, Erik, Olsson, Sandra, Stanne, Tara, Olsson, Martina, Akinyemi, Rufus, Cotlatciuc, Ioana, McArdle, Patrick, Dave, Tushar, Kittner, Steven, Attia, John, Faber, James E, Millwood, Iona, Márquez, Elsa Valdés, Mancuso, Michelangelo, Vibo, Riina, Korv, Janika, Maguire, Jane, Fornage, Myriam, Majersik, Jennifer, DeHavenon, Adam, Alexander, Matthew, Sale, Michele, Southerland, Andrew, Owens, Debra, Psaty, Bruce, Longstreth, W. T., Jr, Wolfe, Stacey Quintero, Langefeld, Carl, Cruchaga, Carlos, Konrad, Jan, Sheth, Kevin, Falcone, Guido, Donahue, Kathleen, Simpkins, Alexis N, Liang Byorn, Tan Wei, Chan, Bernard, Clatworthy, Phil, Florez, Jose, Harshfield, Eric, Hozawa, Atsushi, Hsu, Chung, Hu, Chaur-Jong, Ibanez, Laure, Ihara, Masafumi, Lange, Marcos, Lee, Soo Ji, Lee, I-Hui, Musolino, Patricia, Nakatomi, Hirofumi, Park, Kwang-Yeol, Rich, Stephen S, Riley, Chris, Sung, Joohon, Suzuki, Hideaki, Vo, Katie, Washida, Kazuo, Ibenez, Laura Garcia, Slowik, Agnieszka, Hofman, Albert, Algra, Ale, Reiner, Alex P, Doney, Alexander S F, Gschwendtner, Andreas, Ilinca, Andreea, Giese, Anne-Katrin, Lindgren, Arne, Vicente, Astrid M, Norrving, Bo, Nordestgaard, Børge G, Mitchell, Braxton D, Worrall, Bradford B, Psaty, Bruce M, Carty, Cara L, Sudlow, Cathie, Anderson, Christopher D, Levi, Christopher, Satizabal, Claudia L, Palmer, Colin N A, Gamble, Dale M, Woo, Daniel, Saleheen, Danish, Ringelstein, E Bernd, Valdimarsson, Einar, Holliday, Elizabeth, Davies, Gail, Chauhan, Ganesh, Pasterkamp, Gerard, Boncoraglio, Giorgio, Kuhlenbäumer, Gregor, Thorleifsson, Gudmar, Falcone, Guido J, Pare, Guillame, Schmidt, Helena, Delavaran, Hossein, Markus, Hugh S, Aparicio, Hugo J, Deary, Ian, Cotlarciuc, Ioana, Fernandez-Cadenas, Israel, Meschia, James, Hopewell, Jemma C, Liu, Jingmin, Montaner, Joan, Pera, Joanna, Cole, John, Attia, John R, Rosand, Jonathan, Ferro, Jose M, Bis, Joshua, Furie, Karen, Stefansson, Kari, Berger, Klaus, Kostulas, Konstantinos, Rannikmae, Kristina, Ikram, M Arfan, Benn, Marianne, Dichgans, Martin, Farrall, Martin, Pandolfo, Massimo, Traylor, Matthew, Walters, Matthew, Sale, Michele, Nalls, Mike, Fornage, Myriam, van Zuydam, Natalie R, Sharma, Pankaj, Abrantes, Patricia, de Bakker, Paul IW, Higgins, Peter, Lichtner, Peter, Rothwell, Peter M, Amouyel, Philippe, Yang, Qiong, Malik, Rainer, Schmidt, Reinhold, Clarke, Robert, Lemmens, Robin, van der Laan, Sander W, Pulit, Sara L, Abboud, Sherine, Oliveira, Sofia A, Gretarsdottir, Solveig, Debette, Stephanie, Williams, Stephen R, Bevan, Steve, Kittner, Steven J, Seshadri, Sudha, Mosley, Thomas, Battey, Thomas WK, Tatlisumak, Turgut, Thorsteinsdottir, Unnur, Thijs, Vincent NS, Longstreth, W T, Zhao, Wei, Chen, Wei-Min, Cheng, Yu-Ching, Albert, Marilyn S., Albin, Roger L., Apostolova, Liana G., Arnold, Steven E., Asthana, Sanjay, Atwood, Craig S., Baldwin, Clinton T., Barmada, M. Michael, Barnes, Lisa L., Barral, Sandra, Beach, Thomas G., Becker, James T., Beecham, Gary W., Beekly, Duane, Bennett, David A., Bigio, Eileen H., Bird, Thomas D., Blacker, Deborah, Boeve, Bradley F., Boxer, Adam, Burke, James R., Burns, Jeffrey M., Buxbaum, Joseph D., Byrd, Goldie S., Cai, Guiqing, Cairns, Nigel J., Cantwell, Laura B., Cao, Chuanhai, Carlsson, Cynthia M., Carney, Regina M., Carrasquillo, Minerva M., Carroll, Steven L., Chui, Helena C., Clark, David G., Cribbs, David H., Crocco, Elizabeth A., Cruchaga, Carlos, De Jager, Philip L., DeCarli, Charles, Demirci, F. Yesim, Dick, Malcolm, Dickson, Dennis W., Duara, Ranjan, Ertekin-Taner, Nilufer, Evans, Denis A., Faber, Kelley M., Fallin, M. Daniele, Fallon, Kenneth B., Fardo, David W., Farlow, Martin R., Farrer, Lindsay A., Ferris, Steven, Foroud, Tatiana M., Frosch, Matthew P., Galasko, Douglas R., Gearing, Marla, Geschwind, Daniel H., Ghetti, Bernardino, Gilbert, John R., Go, Rodney C.P., Goate, Alison M., Graff-Radford, Neill R., Green, Robert C., Griffith, Patrick, Growdon, John H., Haines, Jonathan L., Hakonarson, Hakon, Hamilton, Ronald L., Hamilton-Nelson, Kara L., Haroutunian, Vahram, Harrell, Lindy E., Honig, Lawrence S., Huebinger, Ryan M., Hulette, Christine M., Hyman, Bradley T., Jicha, Gregory A., Jin, Lee-Way, Jun, Gyungah, Kamboh, M. Ilyas, Karydas, Anna, Kauwe, John S.K., Kaye, Jeffrey A., Kim, Ronald, Kowall, Neil W., Kramer, Joel H., Kukull, Walter A., Kunkle, Brian W., LaFerla, Frank M., Lah, James J., Lang-Walker, Rosalyn, Larson, Eric B., Leverenz, James B., Levey, Allan I., Li, Ge, Lieberman, Andrew P., Logue, Mark W., Lopez, Oscar L., Lunetta, Kathryn L., Lyketsos, Constantine G., Mack, Wendy J., Manly, Jennifer J., Marson, Daniel C., Martin, Eden R., Martiniuk, Frank, Mash, Deborah C., Masliah, Eliezer, Mayeux, Richard, McKee, Ann C., Mesulam, Marsel, Miller, Bruce L., Miller, Carol A., Miller, Joshua W., Montine, Thomas J., Morris, John C., Murrell, Jill R., Naj, Adam C., Obisesan, Thomas O., Olichney, John M., Pankratz, Vernon S., Parisi, Joseph E., Partch, Amanda, Paulson, Henry L., Pericak-Vance, Margaret A., Perry, William, Peskind, Elaine, Petersen, Ronald C., Pierce, Aimee, Poon, Wayne W., Potter, Huntington, Quinn, Joseph F., Raj, Ashok, Raj, Towfique, Raskind, Murray, Reiman, Eric M., Reisberg, Barry, Reitz, Christiane, Ringman, John M., Roberson, Erik D., Rosen, Howard J., Rosenberg, Roger N., Sager, Mark A., Sano, Mary, Saykin, Andrew J., Schellenberg, Gerard D., Schneider, Julie A., Schneider, Lon S., Seeley, William W., Smith, Amanda G., Sonnen, Joshua A., Spina, Salvatore, Stern, Robert A., Swerdlow, Russell H., Tanzi, Rudolph E., Thornton-Wells, Tricia A., Trojanowski, John Q., Troncoso, Juan C., Tsuang, Debby W., Valladares, Otto, Van Deerlin, Vivianna M., Van Eldik, Linda J., Vardarajan, Badri N., Vinters, Harry V., Vonsattel, Jean Paul, Wang, Li-San, Weintraub, Sandra, Welsh-Bohmer, Kathleen A., Williamson, Jennifer, Wingo, Thomas S., Wishnek, Sarah, Woltjer, Randall L., Wright, Clinton B., Younkin, Steven G., Yu, Chang-En, Yu, Lei, Chauhan, Ganesh, Chu, Audrey Y., Fornage, Myriam, Bis, Joshua C., Havulinna, Aki S., Sargurupremraj, Muralidharan, Smith, Albert Vernon, Adams, Hieab H.H., Choi, Seung Hoan, Trompet, Stella, Garcia, Melissa E., Manichaikul, Ani, Teumer, Alexander, Gustafsson, Stefan, Bartz, Traci M., Bellenguez, Céline, Vidal, Jean Sebastien, Jian, Xueqiu, Kjartansson, Olafur, Wiggins, Kerri L., Satizabal, Claudia L., Xue, Flora, Ripatti, Samuli, Liu, Yongmei, Deelen, Joris, Hoed, Marcel den, Heckbert, Susan R., Rice, Kenneth, Smith, Nicholas L., Wong, Quenna, Aparicio, Hugo J., Buring, Julie E., Ridker, Paul M, Berr, Claudine, Dartigues, Jean-François, Hamsten, Anders, Magnusson, Patrik K., Pedersen, Nancy L., Lannfelt, Lars, Lind, Lars, Lindgren, Cecilia M., Morris, Andrew P., Hofman, Albert, Koudstaal, Peter J., Portegies, Marileen LP., Uitterlinden, André G., de Craen, Anton JM, Ford, Ian, Jukema, J. Wouter, Stott, David J, Allen, Norrina B., Sale, Michele M., Johnson, Andrew D, Bennett, David A., De Jager, Philip L., White, Charles C., Grabe, Hans Jörgen, Paulista Markus, Marcello Ricardo, Lopez, Oscar L, Rotter, Jerome I., Nalls, Michael A., Gottesman, Rebecca F., Griswold, Michael E., Knopman, David S., Windham, B. Gwen, Beiser, Alexa, Vartiainen, Erkki, French, Curtis R., Kurth, Tobias, Psaty, Bruce M., Harris, Tamara B., Rich, Stephen S, deStefano, Anita L., Schmidt, Carsten Oliver, Salomaa, Veikko, Mosley, Thomas H., Ingelsson, Erik, van Duijn, Cornelia M., Tzourio, Christophe, Launer, Lenore J, Ikram, M. Arfan, Chasman, Daniel I., Longstreth, W. T., Jr, Seshadri, Sudha, Debette, Stéphanie, Verhaaren, Benjamin F.J., Debette, Stéphanie, Bis, Joshua C., Smith, Jennifer A., Ikram, M. Kamran, Adams, Hieab H., Beecham, Ashley H., Rajan, Kumar B., Lopez, Lorna M., Barral, Sandra, van Buchem, Mark A., van der Grond, Jeroen, Smith, Albert V., Hegenscheid, Katrin, Aggarwal, Neelum T., de Andrade, Mariza, Atkinson, Elizabeth J., Beekman, Marian, Beiser, Alexa S., Blanton, Susan H., Boerwinkle, Eric, Brickman, Adam M., Bryan, R. Nick, Chauhan, Ganesh, Chen, Christopher P.L.H., Chouraki, Vincent, de Craen, Anton J.M., Crivello, Fabrice, Deary, Ian J., Deelen, Joris, De Jager, Philip L., Dufouil, Carole, Elkind, Mitchell S.V., Evans, Denis A., Freudenberger, Paul, Gottesman, Rebecca F., Guðnason, Vilmundur, Habes, Mohamad, Heckbert, Susan R., Heiss, Gerardo, Hilal, Saima, Hofer, Edith, Hofman, Albert, Ibrahim-Verbaas, Carla A., Knopman, David S., Lewis, Cora E., Liao, Jiemin, Liewald, David C.M., Luciano, Michelle, van der Lugt, Aad, Martinez, Oliver O., Mayeux, Richard, Mazoyer, Bernard, Nalls, Mike, Nauck, Matthias, Niessen, Wiro J., Oostra, Ben A., Psaty, Bruce M., Rice, Kenneth M., Rotter, Jerome I., von Sarnowski, Bettina, Schmidt, Helena, Schreiner, Pamela J., Schuur, Maaike, Sidney, Stephen S., Sigurdsson, Sigurdur, Slagboom, P. Eline, Stott, David J.M., van Swieten, John C., Teumer, Alexander, Töglhofer, Anna Maria, Traylor, Matthew, Trompet, Stella, Turner, Stephen T., Tzourio, Christophe, Uh, Hae-Won, Uitterlinden, André G., Vernooij, Meike W., Wang, Jing J., Wong, Tien Y., Wardlaw, Joanna M., Windham, B. Gwen, Wittfeld, Katharina, Wolf, Christiane, Wright, Clinton B., Yang, Qiong, Zhao, Wei, Zijdenbos, Alex, Jukema, J. Wouter, Sacco, Ralph L., Kardia, Sharon L.R., Amouyel, Philippe, Mosley, Thomas H., Longstreth, W. T., Jr, DeCarli, Charles C., van Duijn, Cornelia M., Schmidt, Reinhold, Launer, Lenore J., Grabe, Hans J., Seshadri, Sudha S., Ikram, M. Arfan, Fornage, Myriam, Bis, Joshua C., Kavousi, Maryam, Franceschini, Nora, Isaacs, Aaron, Abecasis, Gonçalo R, Schminke, Ulf, Post, Wendy, Smith, Albert V., Cupples, L. Adrienne, Markus, Hugh S, Schmidt, Reinhold, Huffman, Jennifer E., Lehtimäki, Terho, Baumert, Jens, Münzel, Thomas, Heckbert, Susan R., Dehghan, Abbas, North, Kari, Oostra, Ben, Bevan, Steve, Stoegerer, Eva-Maria, Hayward, Caroline, Raitakari, Olli, Meisinger, Christa, Schillert, Arne, Sanna, Serena, Völzke, Henry, Cheng, Yu-Ching, Thorsson, Bolli, Fox, Caroline S., Rice, Kenneth, Rivadeneira, Fernando, Nambi, Vijay, Halperin, Eran, Petrovic, Katja E., Peltonen, Leena, Wichmann, H. Erich, Schnabel, Renate B., Dörr, Marcus, Parsa, Afshin, Aspelund, Thor, Demissie, Serkalem, Kathiresan, Sekar, Reilly, Muredach P., Taylor, Kent, Uitterlinden, Andre, Couper, David J., Sitzer, Matthias, Kähönen, Mika, Illig, Thomas, Wild, Philipp S., Orru, Marco, Lüdemann, Jan, Shuldiner, Alan R., Eiriksdottir, Gudny, White, Charles C., Rotter, Jerome I., Hofman, Albert, Seissler, Jochen, Zeller, Tanja, Usala, Gianluca, Ernst, Florian, Launer, Lenore J., DʼAgostino, Ralph B., Sr, OʼLeary, Daniel H., Ballantyne, Christie, Thiery, Joachim, Ziegler, Andreas, Lakatta, Edward G., Chilukoti, Ravi Kumar, Harris, Tamara B., Wolf, Philip A., Psaty, Bruce M., Polak, Joseph F, Li, Xia, Rathmann, Wolfgang, Uda, Manuela, Boerwinkle, Eric, Klopp, Norman, Schmidt, Helena, Wilson, James F, Viikari, Jorma, Koenig, Wolfgang, Blankenberg, Stefan, Newman, Anne B., Witteman, Jacqueline, Heiss, Gerardo, van Duijn, Cornelia, Scuteri, Angelo, Homuth, Georg, Mitchell, Braxton D., Gudnason, Vilmundur, and O’Donnell, Christopher J.

Published
2019
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6. 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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7. Sex-specific Genome Wide Association Study Of Early-onset Ischemic Stroke

Author

Tomppo, Liisa, Rannikmae, Kristiina, Stanne, Tara M., Putaala, Jukka, Strbian, Daniel, Jern, Christina, de Leeuw, Frank Erik, Cadenas, Israel Fernandez, Slowik, Agnieszka M., Boncoraglio, Giorgio, Lindgren, Arne, Conde, Jordi J., Schmidt, Reinhold, Sharma, Pankaj, Lemmens, Robin, Melander, Olle, Rothwell, Peter, Levi, Christopher, Sudlow, Catherine, Debette, Stephanie, Metso, Tiina, Pare, Guillaume, Markus, Hugh, Saleheen, Danish, Danesh, John, Zand, Ramin, Worrall, Bradford B., Meschia, James F., Rundek, Tatjana, Woo, Daniel, Lee, Jin Moo, Irvin, Marguerite R., Mcdonough, Caitrin W., Rexrode, Kathryn M., Wassertheil-Smoller, Sylvia W., Rosand, Jonathan, Gieger, Christian, Muller-Nurasyid, Martina, Salomaa, Veikko V., Kamatani, Yoichiro, Walters, Robin, Chen, Zhengming, Dichgans, Martin, Malik, Rainer, Gaynor, Brady, Cole, John, Xu, Huichun, Mitchell, Braxton D., Kittner, Steven J., Early-Onset Stroke, Consortium, Bordeaux population health (BPH), and Université de Bordeaux (UB)-Institut de Santé Publique, d'Épidémiologie et de Développement (ISPED)-Institut National de la Santé et de la Recherche Médicale (INSERM)

Subjects
Ischemic stroke, Gender differences, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, Genome-wide association studies (GWAS)
Abstract

Introduction: Genetic studies of early-onset disease have been an effective strategy to identify novel pathways and drug targets generalizable also to later-onset disease. Few studies have investigated the sex-specific genetic associations with early-onset ischemic stroke even though several features of ischemic stroke differ between males and females. We hypothesized that stratifying the GWAS by sex would reveal novel stroke loci. Methods: We performed a transethnic ischemic stroke GWAS of 3,056 female cases and 4,462 male cases < 60 years-old and 16,192 and 16,048 sex-matched controls, respectively, from the Early Onset Stroke Genetics Consortium. Results: We identified a significant association in women with a locus in close proximity to TMX1, a transmembrane platelet protein that inhibits platelet function. Additionally, we identified 2 other suggestive (P < 5 x 10-6) loci in females (see Table), i.e., at APOH, which encodes beta2-glycoprotein I, an established GWAS locus for lipoprotein(a), and LRFN2 which has been previously reported to associate with obesity-related measures and type II diabetes. We observed suggestive evidence for association in males with MMP3/MMP12, a known stroke susceptibility locus. Conclusions: Despite a very modest sample size, sex-specific analyses identified suggestive associations at biologically important novel loci in females and a known stroke locus in males. Further studies of sex-specific associations in both early- and later-onset ischemic stroke are needed.

Published
2022
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8. Stroke genetics informs drug discovery and risk prediction across ancestries

Author

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

Abstract

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

Published
2022

9. Whole-exome sequencing in 16,511 individuals reveals a role of the HTRA1 protease and its substrate EGFL8 in brain white matter hyperintensities

Author

Rannikmae, Kristiina, Sudlow, Cathie L M, and Ferguson, Amy

Subjects
HTRA1, SVD, WMH
Abstract

White matter hyperintensities (WMH) are among the most common radiological abnormalities in the ageing population and an established risk factor for stroke and dementia. While common variant association studies have revealed multiple genetic loci with an influence on WMH volume, the contribution of rare variants to WMH burden in the general population remains largely unexplored. We conducted a comprehensive analysis of WMH burden in the UK Biobank using publicly available whole-exome sequencing data (N up to 17,830) and found a splice-site variant in GBE1, encoding 1,4-alpha-glucan branching enzyme 1, to be associated with lower white matter burden on an exome-wide level (c.691+2T>C, beta=-0.74, se=0.13, p=9.7E-9). Applying whole-exome gene-based burden tests, we found damaging missense and loss-of-function variants in HTRA1 (frequency 1 in 275 in the UK Biobank population) to associate with increased WMH volume (p=5.5E-6, FDR=0.04). HTRA1 encodes a secreted serine protease implicated in familial forms of small vessel disease. Domain-specific burden tests revealed that the association with WMH volume was restricted to rare variants in the protease domain (amino acids 204-364; beta=0.79, se=0.14, p=9.4E-8). The frequency of such variants in the UK Biobank population was 1 in 450. WMH volume was brought forward by approximately 11 years in carriers of a rare protease domain variant. A comparison with the effect size of established risk factors for WMH burden revealed that the presence of a rare variant in the HTRA1 protease domain corresponded to a larger effect than meeting the criteria for hypertension (beta=0.26, se=0.02, p=2.9E-59) or being in the upper 99.8% percentile of the distribution of a polygenic risk score based on common genetic variants (beta=0.44, se=0.14, p=0.002). In biochemical experiments, most (6/9) of the identified protease domain variants resulted in a markedly reduced protease activity. We further found EGFL8, which showed suggestive evidence for association with WMH volume (p=1.5E-4, FDR=0.22) in gene burden tests, to be a direct substrate of HTRA1 and to be preferentially expressed in cerebral arterioles and arteries. In a phenome-wide association study (PheWAS) mapping ICD-10 diagnoses to 741 standardized Phecodes, rare variants in the HTRA1 protease domain were associated with multiple neurological and non-neurological conditions including migraine with aura (OR=12.24, 95%CI [2.54-35.25], p=8.3E-5). Collectively, these findings highlight an important role of rare genetic variation and of the HTRA1 protease in determining WMH burden in the general population.

Published
2021
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10. Decreased retinal vascular complexity is an early biomarker of MI supported by a shared genetic control.

Author

Villaplana Velasco, Ana, primary, Engelmann, Justin, additional, Rawlik, Konrad, additional, Canela-Xandri, Oriol, additional, Tochel, Claire, additional, Lona-Durazo, Frida, additional, Mookiah, Muthu Rama Krishnan, additional, Doney, Alexander, additional, Parra, Esteban, additional, Trucco, Emanuele, additional, Macgillivray, Tom, additional, Rannikmae, Kristiina, additional, Tenesa, Albert, additional, Pairo-Castineira, Erola, additional, and Bernabeu, Miguel Oscar, additional

Published
2021
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11. Frequency and phenotype associations of rare variants in five monogenic cerebral small vessel disease genes in 200,000 UK Biobank participants with whole exome sequencing data

Author

Ferguson, Amy C, primary, Thrippleton, Sophie, additional, Henshall, David E, additional, Whittaker, Ed, additional, Conway, Bryan, additional, MacLeod, Malcolm, additional, Malik, Rainer, additional, Rawlik, Konrad, additional, Tenesa, Albert, additional, Sudlow, Cathie, additional, and Rannikmae, Kristiina, additional

Published
2021
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12. Influence of Intracerebral Hemorrhage Location on Incidence, Characteristics, and Outcome: Population-Based Study

Author

Samarasekera, Neshika, Fonville, Arthur, Lerpiniere, Christine, Farrall, Andrew J., Wardlaw, Joanna M., White, Philip M., Smith, Colin, Al-Shahi Salman, Rustam, Addison, Anne, Ahmad, Kate, Alhadad, Syed, Andrews, Peter, Bisset, Elaine, Bodkin, Peter, Bouhaidar, Ralph, Brennan, Paul, Campbell, Brian, Chandran, Siddharthan, Cook, Helen, Davenport, Richard, Dennis, Martin, Derry, Chris, Dodds, Katrina, Doubal, Fergus, Duncan, Susan, Elder, Andrew, Fitzpatrick, Mike, Foley, Peter, Fouyas, Ioannis, Ghosh, Sudipto, Gibson, Rod, Gordon, Claire, Grant, Robin, Hewett, Russell, Hughes, Fiona, Hughes, Mark, Hunt, David, Hunter, Neil, Ironside, James, Liaquat, Imran, Josephson, Colin, Kamat, Anant, Kealley, Susan, Keir, Sarah, Kerr, Gillian, Kerrigan, Simon, Keston, Peter, King, Matthew, Knight, Richard, Macdonald, Elizabeth, Mackay, Graham, Macleod, Donald, Macleod, Malcolm, Maguire, Conor, Makin, Steven, Mathews, Ashok, Maxwell, Fiona, McClellan, Stuart, Millar, Tracey, Morris, Zoe, Morse, Tim, Mumford, Colin, Murray, Katherine, Myles, Lynn, Nimmo, Graham, Ng, Yi, Pal, Suvankar, Rannikmae, Kristiina, Rhodes, Jonathan, Ross, Jerard, Russell, Tim, Sandercock, Peter, Sellar, Robin, Shanmuganathan, Mano, Shekhar, Himanshu, Simms, Henry, Sittampalam, Mara, Soleiman, Hamza, Spiers, Helen, Statham, Patrick, Stavrinos, Neo, Stone, Jon, Stuart, Joyce, Sudlow, Cathie, Summers, David, Taylor, Pat, Torgersen, Antonia, van Dijke, Margarethe, Walker, Robert, Weller, Belinda, Whiteley, William, Whittle, Ian, Will, Robert, Young, Wendy, Anderson, Judith, Broadbent, Seona, Butler, Laura, Caesar, Dave, Cantley, Patricia, Carter, Jonathan, Clegg, Gareth, Coull, Andrew, Crosswaite, Alastair, Dear, James, Dummer, Simon, Duncan, Fiona, Elder-Gracie, Trish, Enright, Kate, Fitzgerald, Tom, Fothergill, Jane, Frier, Brian, Grant, David, Gray, Alasdair, Hart, Simon, Henderson, Robin, Jaap, Alan, Leigh-Smith, Simon, Jones, Michael, Masson, Moyra, McCallum, Lynn, McKechnie, Martin, McKillop, Graham, Mead, Gillian, Morley, Wendy, Morrow, Billie, Morrow, Frank, Murchison, Jon, Murphy, Ross, Ng, Jasmine, Ogundipe, Olayinka, Patel, Dilip, Pollock, Alison, Reed, Matthew, Roberts, Geraint, Selvarajah, Johann, Smith, Randy, Stirling, Claire, Turner, Neil, Wilson, Matthew, Yordanov, Stanko, Bell, Nicola, Chambers, Sarah, Dewar, Sandra, Farquhar, Donald, Harmouche, Ali, Jacob, Ashok, Jackson, Katherine, Knox, Anne, McCafferty, Jon, Moultrie, Sam, Munang, Latana, Noble, Donald, Ramsay, Scott, Spence, Linda, Threlfall, Bethany, Williams, Adrian, Wilson, James, Fitzgerald, Alastair, Jamieson, Andrew, Lange, Peter, McIntosh, Andrew, Morrison, Lewis, and Todd, Iain

Published
2015
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13. Building a Systematic Online Living Evidence Summary of COVID-19 Research

Author

Hair, Kaitlyn, primary, Sena, Emily S., primary, Wilson, Emma, primary, Currie, Gillian, primary, Macleod, Malcolm, primary, Bahor, Zsanett, primary, Sena, Chris, primary, Ayder, Can, primary, Liao, Jing, primary, Tanriver Ayder, Ezgi, primary, Ghanawi, Joly, primary, Tsang, Anthony, primary, Collins, Anne, primary, Carstairs, Alice, primary, Antar, Sarah, primary, Drax, Katie, primary, Neves, Kleber, primary, Ottavi, Thomas, primary, Chow, Yoke Yue, primary, Henry, David, primary, Selli, Cigdem, primary, Fofana, Mariam, primary, Rudnicki, Martina, primary, Gabriel, Brendan, primary, Pearl, Esther J, primary, Kapoor, Simran S, primary, Baginskaite, Julija, primary, Shevade, Santosh, primary, Chung, Alexandria, primary, Przybylska, Marianna Antonia, primary, Henshall, David E, primary, Hajdu, Karina Lôbo, primary, McCann, Sarah, primary, Sutherland, Catherine, primary, Lubiana Alves, Tiago, primary, Blacow, Rachel, primary, Hood, Rebecca J., primary, Soliman, Nadia, primary, Harris, Alison, primary, Swift, Stephanie L., primary, Rackoll, Torsten, primary, Percie du Sert, Nathalie, primary, Waldron, Fergal, primary, Macleod, Magnus, primary, Moulson, Ruth, primary, Low, Juin W., primary, Rannikmae, Kristiina, primary, Miller, Kirsten, primary, Bannach-Brown, Alexandra, primary, Kerr, Fiona, primary, Hébert, Harry L, primary, Gregory, Sarah, primary, Shaw, Isaac William, primary, Christides, Alexander, primary, Alawady, Mohammed, primary, Hillary, Robert, primary, Clark, Alex, primary, Jayasuriya, Natasha, primary, Sives, Samantha, primary, Nazzal, Ahmed, primary, Jayasuriya, Nimesh, primary, Sewell, Michael, primary, Bertani, Rita, primary, Fielding, Helen, primary, and Drury, Broc, primary

Published
2021
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14. Rare Missense Functional Variants at COL4A1 and COL4A2 in Sporadic Intracerebral Hemorrhage

Author

Chung, Jaeyoon, primary, Hamilton, Graham, additional, Kim, Minsup, additional, Marini, Sandro, additional, Montgomery, Bailey, additional, Henry, Jonathan, additional, Cho, Art E., additional, Brown, Devin L., additional, Worrall, Bradford B., additional, Meschia, James F., additional, Silliman, Scott L., additional, Selim, Magdy, additional, Tirschwell, David L., additional, Kidwell, Chelsea S., additional, Kissela, Brett, additional, Greenberg, Steven M., additional, Viswanathan, Anand, additional, Goldstein, Joshua N., additional, Langefeld, Carl D., additional, Rannikmae, Kristiina, additional, Sudlow, Catherine L.M., additional, Samarasekera, Neshika, additional, Rodrigues, Mark, additional, Al-Shahi Salman, Rustam, additional, Prendergast, James G.D., additional, Harris, Sarah E., additional, Deary, Ian, additional, Woo, Daniel, additional, Rosand, Jonathan, additional, Van Agtmael, Tom, additional, and Anderson, Christopher D., additional

Published
2021
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15. Role of Monocyte Chemoattractant Protein-1

Author

Sudlow, Catherine, Worrall, Bradford B, Bernhagen, Jürgen, Malik, Rainer, Dichgans, Martin, Georgakis, Marios K, Gill, Dipender, Rannikmae, Kristiina, Traylor, Matthew, Anderson, Christopher D., Lee, Jin-Moo, Kamatani, Yoichiro, and Hopewell, Jemma C.

Abstract

BACKGROUND: Cytokines and growth factors have been implicated in the initiation and propagation of vascular disease. Observational studies have shown associations of their circulating levels with stroke. Our objective was to explore whether genetically determined circulating levels of cytokines and growth factors are associated with stroke and its etiologic subtypes by conducting a two-sample Mendelian randomization (MR) study.METHODS: Genetic instruments for 41 cytokines and growth factors were obtained from a genome-wide association study (GWAS) of 8,293 healthy adults. Their associations with stroke and stroke subtypes were evaluated in the MEGASTROKE GWAS dataset (67,162 cases; 454,450 controls) applying inverse-variance-weighted meta-analysis, weighted-median analysis, MR-Egger regression, and multivariable MR. The UK Biobank cohort was used as an independent validation sample (4,985 cases; 364,434 controls). Genetic instruments for monocyte chemoattractant protein-1 (MCP-1/CCL2) were further tested for association with etiologically related vascular traits using publicly available GWAS data.RESULTS: Genetic predisposition to higher MCP-1 levels was associated with higher risk of any stroke (OR per 1-SD increase: 1.06, 95% CI: 1.02-1.09, p=0.0009), any ischemic stroke (OR: 1.06, 95% CI: 1.02-1.10, p=0.002), large artery stroke (OR: 1.19, 95% CI: 1.09-1.30, p=0.0002) and cardioembolic stroke (OR: 1.14, 95% CI: 1.06-1.23, p=0.0004), but not with small vessel stroke or intracerebral hemorrhage. The results were stable in sensitivity analyses and remained significant after adjustment for cardiovascular risk factors. Analyses in the UK Biobank showed similar associations for available phenotypes (any stroke: OR: 1.08, 95% CI: 0.99-1.17, p=0.09; any ischemic stroke: OR: 1.07, 95% CI: 0.97-1.18, p=0.17). Genetically determined higher MCP-1 levels were further associated with coronary artery disease (OR: 1.04, 95% CI: 1.00-1.08, p=0.04) and myocardial infarction (OR: 1.05, 95% CI: 1.01-1.09, p=0.02), but not with atrial fibrillation. A meta-analysis of observational studies showed higher circulating MCP-1 levels in stroke patients compared to controls.CONCLUSIONS: Genetic predisposition to elevated circulating levels of MCP-1 is associated with higher risk of stroke, particularly with large artery stroke and cardioembolic stroke. Whether targeting MCP-1 or its receptors can lower stroke incidence requires further study.

Published
2019
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17. Stroke Genetics Network (SiGN) Study: Design and Rationale for a Genome-Wide Association Study of Ischemic Stroke Subtypes

Author

Meschia, James F., Arnett, Donna K., Ay, Hakan, Brown, Robert D., Jr, Benavente, Oscar R., Cole, John W., de Bakker, Paul I.W., Dichgans, Martin, Doheny, Kimberly F., Fornage, Myriam, Grewal, Raji P., Gwinn, Katrina, Jern, Christina, Conde, Jordi Jimenez, Johnson, Julie A., Jood, Katarina, Laurie, Cathy C., Lee, Jin-Moo, Lindgren, Arne, Markus, Hugh S., McArdle, Patrick F., McClure, Leslie A., Mitchell, Braxton D., Schmidt, Reinhold, Rexrode, Kathryn M., Rich, Stephen S., Rosand, Jonathan, Rothwell, Peter M., Rundek, Tatjana, Sacco, Ralph L., Sharma, Pankaj, Shuldiner, Alan R., Slowik, Agnieszka, Wassertheil-Smoller, Sylvia, Sudlow, Cathie, Thijs, Vincent N.S., Woo, Daniel, Worrall, Bradford B., Wu, Ona, Kittner, Steven J., Anderson, Christopher D., Andren, Kerstin, Andsberg, Gunnar, Arsava, Ethem, Barrett, Kevin M., Benner, Thomas, Bentley, Paul, Bevan, Steven, Biffi, Alessandro, Brenner, David, Chapman, Sherita, Cheng, Yu-Ching, Delavaran, Hossein, Deline, Christopher, Dziedzic, Tomasz, Gamble, Dale, Giralt, Eva, Grazer, Anja, Gschwendtner, Andreas, Hegge, Caityln, Heitsch, Laura, Helenius, Johanna, Holmegaard, Lukas, Huq, Mohammed, Irie, Robert E., Jackson, Rebecca, Katschnig, Petra, Katsnelson, Michael, Khoury, Naim, Kilinc, Selma, Kumar, Gyanendra, Labovitz, Daniel, Lanfranconi, Silvia, Langefeld, Carl D., Lemmens, Robin, Li, Linxin, Malik, Shaneela, Melander, Olle, Nordstrom, Sara, Norrving, Bo, Ois, Angel, Ossi, Raid, Peddareddygari, Leema Reddy, Pedersén, Annie, Pera, Joanna, Pucek, Mateusz, Rannikmae, Kristiina, Redfors, Petra, Rhodes, J. David, Ribasés, Marta, Saraf, Neha, Schuerks, Markus, Seiler, Stephan, Sheikh, Huma, Southerland, Andrew M, Sparks, Mary J., Stoegerer, Eva, Sunyer, Jordi, Temple, Ella, Valenti, Raffaella, Weir, David, Weissman, Darren, Woodfield, Rebecca, and Yiin, Gabriel S.C

Published
2013
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18. Association of Apolipoprotein e with Intracerebral Hemorrhage Risk by Race/Ethnicity : A Meta-analysis

Author

Marini, Sandro, Crawford, Katherine, Morotti, Andrea, Lee, Myung J, Pezzini, Alessandro, Moomaw, Charles J, Flaherty, Matthew L, Montaner, Joan, Roquer, Jaume, Jimenez-Conde, Jordi, Giralt-Steinhauer, Eva, Elosua, Roberto, Cuadrado-Godia, Elisa, Soriano-Tarraga, Carolina, Slowik, Agnieszka, Jagiella, Jeremiasz M, Pera, Joanna, Urbanik, Andrzej, Pichler, Alexander, Hansen, Bjorn M, McCauley, Jacob L, Tirschwell, David L, Selim, Magdy, Brown, Devin L, Silliman, Scott L, Worrall, Bradford B, Meschia, James F, Kidwell, Chelsea S, Testai, Fernando D, Kittner, Steven J, Schmidt, Helena, Enzinger, Christian, Deary, Lan J, Rannikmae, Kristiina, Samarasekera, Neshika, Salman, Rustam Al-Shahi, Sudlow, Catherine L, Klijn, Catharina JM, van Nieuwenhuizen, Koen M, Fernandez-Cadenas, Israel, Delgado, Pilar, Nonving, Bo, Lindgren, Ame, Goldstein, Joshua N, Viswanathan, Anand, Greenberg, Steven M, Falcone, Guido J, Biffi, Alessandro, Langefeld, Carl D, Woo, Daniel, Rosand, Jonathan, Anderson, Christopher D, Smoller, Sylvia, Sorkin, John, Wang, Xingwu, Pikula, Aleksandra, Wolf, Philip, Debette, Stephanie, Seshadri, Sudha, de Bakker, Paul, Chasman, Daniel, Rexrode, Kathryn, Chen, Ida, Rotter, Jerome, Luke, May, Sale, Michelle, Lee, Tsong-Hai, Chang, Ku-Chou, Elkind, Mitchell, Goldstein, Larry, James, Michael Luke, Breteler, Monique, O'Donnell, Chris, Leys, Didier, Carty, Cara, Kidwell, Chelsea, Olesen, Jes, Sharma, Pankaj, Rich, Stephen, Tatlisumak, Turgot, Happola, Olli, Bijlenga, Philippe, Soriano, Carolina, Giralt, Eva, Cotlarcius, Loana, Hardy, John, Korostynski, Michal, Boncoraglio, Giorgio, Ballabio, Elena, Parati, Eugenio, Mateusz, Adamski, Dziedzic, Tomasz, Jagiella, Jeremiasz, Gasowski, Jerzy, Wnuk, Marcin, Olszanecki, Rafaf, Juchniewicz, Karol Jozef, Levi, Christopher, Nyquist, Paul, Cendes, Iscia, Cabral, Norberto, Franca, Paulo, Goncalves, Anderson, Keller, Lina, Crisby, Milita, Kostulas, Konstantinos, Lennnnens, Robin, Ahmadi, Kourosh, Opherk, Christian, Duering, Marco, Dichgans, Martin, Malik, Rainer, Gonik, Mariya, Staals, Julie, Melander, Olle, Burri, Philippe, Sadr-Nabavi, Ariane, Romero, Javier, Anderson, Chris, Falcone, Guido, Brouwers, Bart, Rost, Natalia, Du, Rose, Kourkoulis, Christina, Battey, Thomas, Lubitz, Steven, Mueller-Myhsok, Bertram, Meschia, James, Brott, Thomas, Pare, Guillaume, Schmidt, Reinhold, Seiler, Stephan, Blanton, Susan, Yamada, Yoshiji, Bersano, Anna, Rundek, Tatiana, Sacco, Ralph, Chan, Yu-Feng Yvonne, Gschwendtner, Andreas, Deng, Zhen, Barr, Taura, Gwinn, Katrina, Corriveau, Roderick, Singleton, Andrew, Waddy, Salina, Launer, Lenore, Chen, Christopher, Le, Kim En, Lee, Wei Ling, Tan, Eng King, Olugbodi, Akintomi, Rothwell, Peter, Schilling, Sabrina, Mok, Vincent, Lebedeva, Elena, Jem, Christina, Jood, Katarina, Olsson, Sandra, Kim, Helen, Lee, Chaeyoung, Kilarski, Laura, Markus, Hugh, Peycke, Jennifer, Bevan, Steve, Sheu, Wayne, Chiou, Hung Yi, Chern, Joseph, Giraldo, Elias, Taqi, Muhammad, Jain, Vivek, Lam, Olivia, Howard, George, Kittner, Steven, Mitchell, Braxton, Cole, John, O'Connell, Jeff, Milewicz, Dianna, Illoh, Kachikwu, Worrall, Bradford, Stine, Colin, Karaszewski, Bartosz, Werring, David, Sofat, Reecha, Smalley, June, Lindgren, Arne, Hansen, Bjorn, Norrving, Bo, Smith, Gustav, Martin, Juan Jose, Thijs, Vincent, Klijn, Karin, van't Hof, Femke, Algra, Ale, Macleod, Mary, Perry, Rodney, Arnett, Donna, Padovani, Alessandro, Cramer, Steve, Fisher, Marl, Saleheen, Danish, Broderick, Joseph, Kissela, Brett, Doney, Alex, Sudlow, Cathie, Silliman, Scott, McDonough, Caitrin, Walters, Matthew, Pedersen, Annie, Nakagawa, Kazuma, Chang, Christy, Dobbins, Mark, McArdle, Patrick, Chang, Yu-Ching, Brown, Robert, Brown, Devin, Holliday, Elizabeth, Kalaria, Raj, Maguire, Jane, Hunter, John, Attia, John, Farrall, Martin, Giese, Anne-Katrin, Fomage, Myriam, Majersik, Jennifer, Cushman, Maly, Keene, Keith, Bennett, Siiri, Tirschwell, David, Psaty, Bruce, Reiner, Alex, Longstreth, Will, Spence, David, Langefeld, Carl, Bushnell, Cheryl, Heitsch, Laura, Lee, Jin-Moo, Sheth, Kevin, Consortium, Int Genetics, Neurologian yksikkö, Department of Neurosciences, Clinicum, Doctoral Programme in Clinical Research, HUS Neurocenter, RS: Carim - B05 Cerebral small vessel disease, RS: CARIM - R3.03 - Cerebral small vessel disease, and Epidemiology

Subjects
Male, Race ethnicity, Hemorràgia cerebral, 3124 Neurology and psychiatry, 0302 clinical medicine, Risk Factors, WHITES, BLACKS, 030212 general & internal medicine, Biological sciences, Original Investigation, ALZHEIMER-DISEASE, African Americans, Aged, 80 and over, GENETIC-VARIATION, Hispanic or Latino, Middle Aged, Disorders of movement Donders Center for Medical Neuroscience [Radboudumc 3], Medical research, University hospital, 3. Good health, ETHNICITY, ALLELE, Research centre, Hypertension, lipids (amino acids, peptides, and proteins), Female, Apolipoprotein E, Core laboratory, Hispanic Americans, medicine.medical_specialty, COA REDUCTASE INHIBITORS, European Continental Ancestry Group, Clinical Neurology, Raça, APOE EPSILON-4, White People, 03 medical and health sciences, All institutes and research themes of the Radboud University Medical Center, Apolipoproteins E, Political science, medicine, Journal Article, Online First, Humans, Genetic Predisposition to Disease, cardiovascular diseases, General hospital, Aged, Cerebral Hemorrhage, Research, LOBAR, 3112 Neurosciences, E GENOTYPE, United States, nervous system diseases, Black or African American, Cognitive epidemiology, Family medicine, Case-Control Studies, Neurology (clinical), 030217 neurology & neurosurgery
Abstract

Key Points Question Is history of hypertension and apolipoprotein E (APOE) associated with intracerebral hemorrhage risk in participants stratified by self-reported race/ethnicity? Findings In this case-control study of 13 124 adults, having a copy of APOE ε4 alleles increased the risk for lobar intracerebral hemorrhage only in white individuals, but after propensity score matching for hypertension burden, Hispanic individuals showed the same risk of APOE ε4. Meaning APOE ε4 appears to be confirmed as a risk factor for lobar intracerebral hemorrhage in nonwhite populations but is masked by differential hypertension burden in Hispanic individuals; further studies are needed to explore the interactions between APOE alleles and environmental exposures., Importance Genetic studies of intracerebral hemorrhage (ICH) have focused mainly on white participants, but genetic risk may vary or could be concealed by differing nongenetic coexposures in nonwhite populations. Transethnic analysis of risk may clarify the role of genetics in ICH risk across populations. Objective To evaluate associations between established differences in ICH risk by race/ethnicity and the variability in the risks of apolipoprotein E (APOE) ε4 alleles, the most potent genetic risk factor for ICH. Design, Setting, and Participants This case-control study of primary ICH meta-analyzed the association of APOE allele status on ICH risk, applying a 2-stage clustering approach based on race/ethnicity and stratified by a contributing study. A propensity score analysis was used to model the association of APOE with the burden of hypertension across race/ethnic groups. Primary ICH cases and controls were collected from 3 hospital- and population-based studies in the United States and 8 in European sites in the International Stroke Genetic Consortium. Participants were enrolled from January 1, 1999, to December 31, 2017. Participants with secondary causes of ICH were excluded from enrollment. Controls were regionally matched within each participating study. Main Outcomes and Measures Clinical variables were systematically obtained from structured interviews within each site. APOE genotype was centrally determined for all studies. Results In total, 13 124 participants (7153 [54.5%] male with a median [interquartile range] age of 66 [56-76] years) were included. In white participants, APOE ε2 (odds ratio [OR], 1.49; 95% CI, 1.24-1.80; P, This case-control study examines whether the risk for intracerebral hemorrhage presented by apolipoprotein E ε4 and ε2 alleles varies by race/ethnicity.

Published
2019
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19. Relative effects of LDL-C on ischemic stroke and coronary disease A Mendelian randomization study

Author

Valdes-Marquez, Elsa, Parish, Sarah, Clarke, Robert, Stari, Traiani, Worrall, Bradford B, Hopewell, Jemma C, Slowik, Agnieszka, Hofman, Albert, Algra, Ale, Reiner, Alex P, Doney, Alexander SF, Gschwendtner, Andreas, Ilinca, Andreea, Giese, Anne-Katrin, Lindgren, Arne, Vicente, Astrid M, Norrving, Bo, Nordestgaard, Borge G, Mitchell, Braxton D, Psaty, Bruce M, Carty, Cara L, Sudlow, Cathie LM, Anderson, Christopher, Levi, Christopher R, Satizabal, Claudia L, Palmer, Colin NA, Gamble, Dale M, Woo, Daniel, Saleheen, Danish, Ringelstein, Bernd E, Valdimarsson, Einar M, Holliday, Elizabeth G, Davies, Gail, Chauhan, Ganesh, Pasterkamp, Gerard, Boncoraglio, Giorgio B, Kuhlenbaeumer, Gregor, Thorleifsson, Gudmar, Falcone, Guido J, Pare, Guillaume, Schmidt, Helena, Delavaran, Hossein, Markus, Hugh S, Aparicio, Hugo J, Deary, Ian, Cotlarciuc, Ioana, Fernandez-Cadenas, Israel, Meschia, James F, Liu, Jingmin, Montaner, Joan, Pera, Joanna, Cole, John, Attia, John R, Rosand, Jonathan, Ferro, Jose M, Bis, Joshua C, Furie, Karen, Stefansson, Kari, Berger, Klaus, Kostulas, Konstantinos, Rannikmae, Kristiina, Ikram, Arfan M, Benn, Marianne, Dichgans, Martin, Pandolfo, Massimo, Traylor, Matthew, Walters, Matthew, Sale, Michele, Nalls, Michael A, Fornage, Myriam, van Zuydam, Natalie R, Sharma, Pankaj, Abrantes, Patricia, de Bakker, Paul IW, Higgins, Peter, Lichtner, Peter, Rothwell, Peter M, Amouyel, Philippe, Yang, Qiong, Malik, Rainer, Schmidt, Reinhold, Lemmens, Robin, van der Laan, Sander W, Pulit, Sara L, Abboud, Sherine, Oliveira, Sofia A, Gretarsdottir, Solveig, Debette, Stephanie, Williams, Stephen R, Bevan, Steve, Kittner, Steven J, Seshadri, Sudha, Mosley, Thomas, Battey, Thomas WK, Tatlisumak, Turgut, Thorsteinsdottir, Unnur, Thijs, Vincent NS, Longstreth, WT, Zhao, Wei, Chen, Wei-Min, and Cheng, Yu-Ching

Subjects
Science & Technology, STATIN THERAPY, DENSITY-LIPOPROTEIN-CHOLESTEROL, Clinical Neurology, HEART-DISEASE, SUBTYPES, PCSK9, Centre for Brain Research, REDUCTION, BMI, GENETIC-VARIANTS, RISK-FACTORS, Neurosciences & Neurology, Life Sciences & Biomedicine, METAANALYSIS
Abstract

OBJECTIVE: To examine the causal relevance of lifelong differences in low-density lipoprotein cholesterol (LDL-C) for ischemic stroke (IS) relative to that for coronary heart disease (CHD) using a Mendelian randomization approach. METHODS: We undertook a 2-sample Mendelian randomization, based on summary data, to estimate the causal relevance of LDL-C for risk of IS and CHD. Information from 62 independent genetic variants with genome-wide significant effects on LDL-C levels was used to estimate the causal effects of LDL-C for IS and IS subtypes (based on 12,389 IS cases from METASTROKE) and for CHD (based on 60,801 cases from CARDIoGRAMplusC4D). We then assessed the effects of LDL-C on IS and CHD for heterogeneity. RESULTS: A 1 mmol/L higher genetically determined LDL-C was associated with a 50% higher risk of CHD (odds ratio [OR] 1.49, 95% confidence interval [CI] 1.32-1.68, p = 1.1 × 10-8). By contrast, the causal effect of LDL-C was much weaker for IS (OR 1.12, 95% CI 0.96-1.30, p = 0.14; p for heterogeneity = 2.6 × 10-3) and, in particular, for cardioembolic stroke (OR 1.06, 95% CI 0.84-1.33, p = 0.64; p for heterogeneity = 8.6 × 10-3) when compared with that for CHD. CONCLUSIONS: In contrast with the consistent effects of LDL-C-lowering therapies on IS and CHD, genetic variants that confer lifelong LDL-C differences show a weaker effect on IS than on CHD. The relevance of etiologically distinct IS subtypes may contribute to the differences observed. ispartof: NEUROLOGY vol:92 issue:11 pages:E1176-E1187 ispartof: location:United States status: published

Published
2019

20. Association of apolipoprotein E with intracerebral hemorrhage risk by race/ethnicity

Author

Marini, Sandro, Crawford, Katherine, Morotti, Andrea, Lee, Myung, Pezzini, Alessandro, Moomaw, Charles, Flaherty, Matthew, Montaner, Joan, Roquer, Jaume, Jimenez-Conde, Jordi, Giralt-Steinhauer, Eva, Elosua, Roberto, Cuadrado-Godia, Elisa, Soriano-Tarraga, Carolina, Słowik, Agnieszka, Jagiełła, Jeremiasz, Pera, Joanna, Urbanik, Andrzej, Pichler, Alexander, Hansen, Bjorn, McCauley, Jacob, Tirschwell, David, Selim, Magdy, Brown, Devin, Silliman, Scott, Worrall, Bradford, Meschia, James, Kidwell, Chelsea, Testai, Fernando, Kittner, Steven, Schmidt, Helena, Enzinger, Christian, Deary, Ian, Rannikmae, Kristiina, Samarasekera, Neshika, Al-Shahi Salman, Rustam, Sudlow, Catherine, Klijn, Catharina, van Nieuwenhuizen, Koen, Fernandez-Cadenas, Israel, Delgado, Pilar, Norrving, Bo, Lindgren, Arne, Goldstein, Joshua, Viswanathan, Anand, Greenberg, Steven, Falcone, Guido, Biffi, Alessandro, Langefeld, Carl, Woo, Daniel, Rosand, Jonathan, Anderson, Christopher, National Institute of Neurological Disorders and Stroke (US), Neurocritical Care Society (US), American Heart Association, Medical Research Council (UK), Age UK, Centre for Cognitive Ageing and Cognitive Epidemiology (UK), Wellcome Trust, Binks Trust, Scottish Funding Council, Chief Scientist Office (UK), Swedish Heart-Lung Foundation, Skåne Regional Council, Skåne University Hospital, The Grand Lodge of Sweden, King Gustaf V and Queen Victoria's Foundation, Lund University, Foundation of Färs & Frosta, Swedish Stroke Association, Ministerio de Sanidad, Servicios Sociales e Igualdad (España), Instituto de Salud Carlos III, and European Commission

Subjects
education, cardiovascular diseases, nervous system diseases
Abstract

[Importance] Genetic studies of intracerebral hemorrhage (ICH) have focused mainly on white participants, but genetic risk may vary or could be concealed by differing nongenetic coexposures in nonwhite populations. Transethnic analysis of risk may clarify the role of genetics in ICH risk across populations., [Objective] To evaluate associations between established differences in ICH risk by race/ethnicity and the variability in the risks of apolipoprotein E (APOE) ε4 alleles, the most potent genetic risk factor for ICH., [Design, Setting, and Participants] This case-control study of primary ICH meta-analyzed the association of APOE allele status on ICH risk, applying a 2-stage clustering approach based on race/ethnicity and stratified by a contributing study. A propensity score analysis was used to model the association of APOE with the burden of hypertension across race/ethnic groups. Primary ICH cases and controls were collected from 3 hospital- and population-based studies in the United States and 8 in European sites in the International Stroke Genetic Consortium. Participants were enrolled from January 1, 1999, to December 31, 2017. Participants with secondary causes of ICH were excluded from enrollment. Controls were regionally matched within each participating study., [Main Outcomes and Measures] Clinical variables were systematically obtained from structured interviews within each site. APOE genotype was centrally determined for all studies., [Results] In total, 13 124 participants (7153 [54.5%] male with a median [interquartile range] age of 66 [56-76] years) were included. In white participants, APOE ε2 (odds ratio [OR], 1.49; 95% CI, 1.24-1.80; P, [Conclusions and Relevance] APOE ε4 and ε2 alleles appear to affect lobar ICH risk variably by race/ethnicity, associations that are confirmed in white individuals but can be shown in Hispanic individuals only when the excess burden of hypertension is propensity score–matched; further studies are needed to explore the interactions between APOE alleles and environmental exposures that vary by race/ethnicity in representative populations at risk for ICH., This study was funded by grants K23NS086873, R01NS103924, U01NS069763, R01NS093870, R01AG047975, R01AG026484, P50AG005134, and K23AG02872605 from the NIH National Institute of Neurological Disorders and Stroke; a Yale Pepper Scholar Award (P30AG021342) and the Neurocritical Care Society Research Fellowship (Dr Falcone); an American Heart Association fellowship (18POST34080063) (Dr Marini); and a United Kingdom Medical Research Council/Stroke Association Clinical Research Training Fellowship and a United Kingdom Medical Research Council Senior Clinical Fellowship. The Lothian Birth Cohort 1936 is supported by Age UK (The Disconnected Mind project), the Medical Research Council (MR/M01311/1), and the Centre for Cognitive Ageing and Cognitive Epidemiology (which is funded by the Medical Research Council and the Biotechnology and Biological Sciences Research Council [MR/K026992/1]). The Edinburgh Stroke Study was supported by the Wellcome Trust and the Binks Trust. Sample processing occurred in the Genetics Core Laboratory of the Wellcome Trust Clinical Research Facility, Western General Hospital. Much of the neuroimaging occurred in the Scottish Funding Council Brain Imaging Research Centre, University of Edinburgh, a core area of the Wellcome Trust Clinical Research Facility and part of the Scottish Imaging Network–A Platform for Scientific Excellence collaboration (funded by the Scottish Funding Council and the Chief Scientist Office). Lund Stroke Register is supported by the Swedish Heart and Lung Foundation, Region Skåne, Skåne University Hospital, the Freemasons Lodge of Instruction EOS in Lund, King Gustaf V and Queen Victoria’s Foundation, Lund University, the Foundation of Färs & Frosta (one of Sparbanken Skåne’s ownership Foundations), and the Swedish Stroke Association. ICH case and control recruitment from Spain has been supported by the Spain Ministry of Health Instituto de Salud Carlos III FEDER RD16/0019/0002.INVICTUS-PLUS.

Published
2019

21. Atrial fibrillation genetic risk differentiates cardioembolic stroke from other stroke subtypes

Author

Pulit, Sara L., Weng, Lu-Chen, McArdle, Patrick F, Trinquart, Ludovic, Choi, Seung Hoan, Mitchell, Braxton D., Rosand, Jonathan, de Bakker, Paul I W, Benjamin, Emelia J, Ellinor, Patrick T, Kittner, Steven J, Lubitz, Steven A, Anderson, Christopher D, Christophersen, Ingrid E., Rienstra, Michiel, Roselli, Carolina, Yin, Xiaoyan, Geelhoed, Bastiaan, Barnard, John, Lin, Honghuang, Arking, Dan E., Smith, Albert V., Albert, Christine M., Chaffin, Mark, Tucker, Nathan R., Li, Molong, Klarin, Derek, Bihlmeyer, Nathan A, Low, Siew-Kee, Weeke, Peter E., Müller-Nurasyid, Martina, Smith, J. Gustav, Brody, Jennifer A., Niemeijer, Maartje N., Dörr, Marcus, Trompet, Stella, Huffman, Jennifer, Gustafsson, Stefan, Schurmann, Claudia, Kleber, Marcus E., Lyytikäinen, Leo-Pekka, Seppälä, Ilkka, Malik, Rainer, Horimoto, Andrea R. V. R., Perez, Marco, Sinisalo, Juha, Aeschbacher, Stefanie, Thériault, Sébastien, Yao, Jie, Radmanesh, Farid, Weiss, Stefan, Teumer, Alexander, Clauss, Sebastian, Deo, Rajat, Rader, Daniel J., Shah, Svati, Siland, Joylene E., Kubo, Michiaki, Smith, Jonathan D., Van Wagoner, David R., Bis, Joshua C., Perz, Siegfried, Psaty, Bruce M., Ridker, Paul M., Magnani, Jared W., Harris, Tamara B., Launer, Lenore J., Shoemaker, M. Benjamin, Padmanabhan, Sandosh, Haessler, Jeffrey, Bartz, Traci M., Waldenberger, Melanie, Lichtner, Peter, Arendt, Marina, Krieger, Jose E., Kähönen, Mika, Risch, Lorenz, Mansur, Alfredo J., Peters, Annette, Smith, Blair H., Lind, Lars, Scott, Stuart A., Lu, Yingchang, Bottinger, Erwin B., Hernesniemi, Jussi, Lindgren, Cecilia M., Wong, Jorge A, Huang, Jie, Eskola, Markku, Morris, Andrew P., Ford, Ian, Reiner, Alex P., Delgado, Graciela, Chen, Lin Y., Chen, Yii-Der Ida, Sandhu, Roopinder K., Li, Man, Boerwinkle, Eric, Eisele, Lewin, Lannfelt, Lars, Rost, Natalia, Orho-Melander, arju, Hamsten, Anders, Heeringa, Jan, Denny, Joshua C., Kriebel, Jennifer, Darbar, Dawood, Newton-Cheh, Christopher, Shaffer, Christian, Macfarlane, Peter W., Heilmann, Stefanie, Almgren, Peter, Huang, Paul L., Sotoodehnia, Nona, Soliman, Elsayed Z., Uitterlinden, Andre G., Hofman, Albert, Franco, Oscar H., Völker, Uwe, Jöckel, Karl-Heinz, Sinner, Moritz F., Lin, Henry J., Guo, Xiuqing, Dichgans, Martin, Ingelsson, Erik, Kooperberg, Charles, Melander, Olle, Loos, Ruth J. F., Laurikka, Jari, Conen, David, Harst, Pim van der, Lokki, Marja-Liisa, Kathiresan, Sekar, Pereira, Alexandre, Jukema, J. Wouter, Hayward, Caroline, Rotter, Jerome I., März, Winfried, Lehtimäki, Terho, Stricker, Bruno H., Chung, Mina K., Felix, Stephan B., Gudnason, Vilmundur, Alonso, Alvaro, Roden, Dan M., Sun, Albert, Anderson, Christopher D., Kääb, Stefan, Hopewell, Jemma C., Debette, Stephanie, Chauhan, Ganesh, Yang, Qiong, Worrall, Bradford B., Paré, Guillaume, Kamatani, Yoichiro, Hagemeijer, Yanick P., Verweij, Niek, Taylor, Kent D., Campbell, Archie, Magnusson, Patrik K., Porteous, David, Hocking, Lynne J., Vlachopoulou, Efthymia, Pedersen, Nancy L., Nikus, Kjell, Chasman, Daniel I., Heckbert, Susan R., Benjamin, Emelia J., Tanaka, Toshihiro, Lunetta, Kathryn L., Lubitz, Steven A., Ellinor, Patrick T., Smoller, Sylvia, Sorkin, John, Wang, Xingwu, Selim, Magdy, Pikula, Aleksandra, Wolf, Philip, Seshadri, Sudha, Bakker, Paul de, Chasman, Daniel, Rexrode, Kathryn, Chen, Ida, Rotter, Jerome, Luke, May, Sale, Michelle, Lee, Tsong-Hai, Chang, Ku-Chou, Elkind, Mitchell, Goldstein, Larry, James, Michael Luke, Breteler, Monique, O’Donnell, Chris, Leys, Didier, Carty, Cara, Kidwell, Chelsea, Olesen, Jes, Sharma, Pankaj, Rich, Stephen, Tatlisumak, Turgot, Happola, Olli, Bijlenga, Philippe, Soriano, Carolina, Giralt, Eva, Roquer, Jaume, Jimenez-Conde, Jordi, Cotlarcius, Ioana, Hardy, John, Korostynski, Michal, Boncoraglio, Giorgio, Ballabio, Elena, Parati, Eugenio, Mateusz, Adamski, Urbanik, Andrzej, Dziedzic, Tomasz, Jagiella, Jeremiasz, Gasowski, Jerzy, Wnuk, Marcin, Olszanecki, Rafael, Pera, Joanna, Slowik, Agnieszka, Juchniewicz, Karol Jozef, Levi, Christopher, Nyquist, Paul, Cendes, Iscia, Cabral, Norberto, Franca, Paulo, Goncalves, Anderson, Keller, Lina, Crisby, Milita, Kostulas, Konstantinos, Lemmens, Robin, Ahmadi, Kourosh, Opherk, Christian, Duering, Marco, Gonik, Mariya, Staals, Julie, Burri, Philippe, Sadr-Nabavi, Ariane, Romero, Javier, Biffi, Alessandro, Anderson, Chris, Falcone, Guido, Brouwers, Bart, Du, Rose, Kourkoulis, Christina, Battey, Thomas, Lubitz, Steven, Mueller-Myhsok, Bertram, Meschia, James, Brott, Thomas, Pare, Guillaume, Pichler, Alexander, Enzinger, Christian, Schmidt, Helena, Schmidt, Reinhold, Seiler, Stephan, Blanton, Susan, Yamada, Yoshiji, Bersano, Anna, Rundek, Tatjana, Sacco, Ralph, Chan, Yu-Feng Yvonne, Gschwendtner, Andreas, Deng, Zhen, Barr, Taura, Gwinn, Katrina, Corriveau, Roderick, Singleton, Andrew, Waddy, Salina, Launer, Lenore, Chen, Christopher, Le, Kim En, Lee, Wei Ling, Tan, Eng King, Olugbodi, Akintomi, Rothwell, Peter, Schilling, Sabrina, Mok, Vincent, Lebedeva, Elena, Jern, Christina, Jood, Katarina, Olsson, Sandra, Kim, Helen, Lee, Chaeyoung, Kilarski, Laura, Markus, Hugh, Peycke, Jennifer, Bevan, Steve, Sheu, Wayne, Chiou, Hung Yi, Chern, Joseph, Giraldo, Elias, Taqi, Muhammad, Jain, Vivek, Lam, Olivia, Howard, George, Woo, Daniel, Kittner, Steven, Mitchell, Braxton, Cole, John, O’Connell, Jeff, Milewicz, Dianna, Illoh, Kachikwu, Worrall, Bradford, Stine, Colin, Karaszewski, Bartosz, Werring, David, Sofat, Reecha, Smalley, June, Lindgren, Arne, Hansen, Bjorn, Norrving, Bo, Smith, Gustav, Martin, Juan Jose, Thijs, Vincent, Klijn, Karin, van’t Hof, Femke, Algra, Ale, Macleod, Mary, Perry, Rodney, Arnett, Donna, Pezzini, Alessandro, Padovani, Alessandro, Cramer, Steve, Fisher, Mark, Saleheen, Danish, Broderick, Joseph, Kissela, Brett, Doney, Alex, Cathie, Sudlow, Rannikmae, Kristiina, Silliman, Scott, McDonough, Caitrin, Walters, Matthew, Pedersen, Annie, Nakagawa, Kazuma, Chang, Christy, Dobbins, Mark, McArdle, Patrick, Chang, Yu-Ching, Brown, Robert, Brown, Devin, Holliday, Elizabeth, Kalaria, Raj, Maguire, Jane, John, Attia, Farrall, Martin, Giese, Anne-Katrin, Fornage, Myriam, Majersik, Jennifer, Cushman, Mary, Keene, Keith, Bennett, Siiri, Tirschwell, David, Psaty, Bruce, Reiner, Alex, Longstreth, Will, Spence, David, Montaner, Joan, Fernandez-Cadenas, Israel, Langefeld, Carl, Bushnell, Cheryl, Heitsch, Laura, Lee, Jin-Moo, Sheth, Kevin, Cardiovascular Centre (CVC), Department of Medicine, Clinicum, Transplantation Laboratory, Medicum, Neurologian yksikkö, Department of Neurosciences, University of Helsinki, Doctoral Programme in Clinical Research, HUS Neurocenter, Epidemiology, Internal Medicine, Klinische Neurowetenschappen, RS: CARIM - R3.03 - Cerebral small vessel disease, and MUMC+: MA Med Staf Spec Neurologie (9)

Subjects
Medizin, 030204 cardiovascular system & hematology, VARIANTS, 3124 Neurology and psychiatry, 0302 clinical medicine, Epidemiology, Genotype, EPIDEMIOLOGY, Stroke, Genetics (clinical), 0303 health sciences, Aspirin, Atrial fibrillation, ASSOCIATION, 3. Good health, LIFETIME RISK, ISCHEMIC-STROKE, Cardiology, Biomarker (medicine), Medical genetics, BURDEN, Medical Genetics, Life Sciences & Biomedicine, medicine.drug, medicine.medical_specialty, Clinical Neurology, Single-nucleotide polymorphism, Article, 03 medical and health sciences, Internal medicine, Genetic predisposition, medicine, SNP, cardiovascular diseases, Genotyping, 030304 developmental biology, Genetic association, Medicinsk genetik, Science & Technology, business.industry, 3112 Neurosciences, Heritability, medicine.disease, PREVENTION, ASPIRIN, Neurology (clinical), Neurosciences & Neurology, business, 030217 neurology & neurosurgery, CAUSATIVE CLASSIFICATION
Abstract

ObjectiveWe sought to assess whether genetic risk factors for atrial fibrillation (AF) can explain cardioembolic stroke risk.MethodsWe evaluated genetic correlations between a previous genetic study of AF and AF in the presence of cardioembolic stroke using genome-wide genotypes from the Stroke Genetics Network (N = 3,190 AF cases, 3,000 cardioembolic stroke cases, and 28,026 referents). We tested whether a previously validated AF polygenic risk score (PRS) associated with cardioembolic and other stroke subtypes after accounting for AF clinical risk factors.ResultsWe observed a strong correlation between previously reported genetic risk for AF, AF in the presence of stroke, and cardioembolic stroke (Pearson r = 0.77 and 0.76, respectively, across SNPs with p < 4.4 × 10−4 in the previous AF meta-analysis). An AF PRS, adjusted for clinical AF risk factors, was associated with cardioembolic stroke (odds ratio [OR] per SD = 1.40, p = 1.45 × 10−48), explaining ∼20% of the heritable component of cardioembolic stroke risk. The AF PRS was also associated with stroke of undetermined cause (OR per SD = 1.07, p = 0.004), but no other primary stroke subtypes (all p > 0.1).ConclusionsGenetic risk of AF is associated with cardioembolic stroke, independent of clinical risk factors. Studies are warranted to determine whether AF genetic risk can serve as a biomarker for strokes caused by AF.

Published
2018

22. Multiancestry genome-wide association study of 520,000 subjects identifies 32 loci associated with stroke and stroke subtypes

Author

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 H. H., Ago, Tetsuro, Almgren, Peter, Amouyel, Philippe, Ay, Hakan, Bartz, Traci M., Benavente, Oscar R., Bevan, Steve, Boncoraglio, Giorgio B., Brown, Robert D., Jr., Butterworth, Adam S., Carrera, Caty, Carty, Cara L., Chasman, Daniel I., Chen, Wei-Min, Cole, John W., Correa, Adolfo, Cotlarciuc, Ioana, Cruchaga, Carlos, Danesh, John, de Bakker, Paul I. W., DeStefano, Anita L., den Hoed, Marcel, Duan, Qing, Engelter, Stefan T., Falcone, Guido J., Gottesman, Rebecca F., Grewal, Raji P., Gudnason, Vilmundur, Gustafsson, Stefan, Haessler, Jeffrey, Harris, Tamara B., Hassan, Ahamad, Havulinna, Aki S., Heckbert, Susan R., Holliday, Elizabeth G., Howard, George, Hsu, Fang-Chi, Hyacinth, Hyacinth I., Ikram, M. Arfan, Ingelsson, Erik, Irvin, Marguerite R., Jian, Xueqiu, Jimenez-Conde, Jordi, Johnson, Julie A., Jukema, J. Wouter, Kanai, Masahiro, Keene, Keith L., Kissela, Brett M., Kleindorfer, Dawn O., Kooperberg, Charles, 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., Psaty, Bruce M., Pulit, Sara L., Rannikmae, Kristiina, Reiner, Alexander P., Rexrode, Kathryn M., Rice, Kenneth, Rich, Stephen S., Ridker, Paul M., Rost, Natalia S., Rothwell, Peter M., Rotter, Jerome I., 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 L. M., Tanislav, Christian, Tatlisumak, Turgut, Taylor, Kent D., Thijs, Vincent N. S., Thorleifsson, Gudmar, Thorsteinsdottir, Unnur, Tiedt, Steffen, Trompet, Stella, Tzourio, Christophe, van Duijn, Cornelia M., Walters, Matthew, Wareham, Nicholas J., Wassertheil-Smoller, Sylvia, Wilson, James G., Wiggins, Kerri L., Yang, Qiong, Yusuf, Salim, Bis, Joshua C., Pastinen, Tomi, Ruusalepp, Arno, Schadt, Eric E., Koplev, Simon, Bjorkegren, Johan L. M., Codoni, Veronica, Civelek, Mete, Smith, Nicholas L., Tregouet, David A., Christophersen, Ingrid E., Roselli, Carolina, Lubitz, Steven A., Ellinor, Patrick T., Tai, E. Shyong, Kooner, Jaspal S., Kato, Norihiro, He, Jiang, van der Harst, Pim, Elliott, Paul, Chambers, John C., Takeuchi, Fumihiko, Johnson, Andrew D., Sanghera, Dharambir K., Melander, Olle, Jern, Christina, Strbian, Daniel, Fernandez-Cadenas, Israel, Longstreth, W. T., Jr., Rolfs, Arndt, Hata, Jun, Woo, Daniel, Rosand, Jonathan, Pare, Guillaume, Hopewell, Jemma C., Ingelsson, Martin, Saleheen, Danish, Stefansson, Kari, Worrall, Bradford B., Kittner, Steven J., Seshadri, Sudha, Fornage, Myriam, Lind, Lars, Markus, Hugh S., Howson, Joanna M. M., Kamatani, Yoichiro, Debette, Stephanie, Dichgans, Martin, 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 H. H., Ago, Tetsuro, Almgren, Peter, Amouyel, Philippe, Ay, Hakan, Bartz, Traci M., Benavente, Oscar R., Bevan, Steve, Boncoraglio, Giorgio B., Brown, Robert D., Jr., Butterworth, Adam S., Carrera, Caty, Carty, Cara L., Chasman, Daniel I., Chen, Wei-Min, Cole, John W., Correa, Adolfo, Cotlarciuc, Ioana, Cruchaga, Carlos, Danesh, John, de Bakker, Paul I. W., DeStefano, Anita L., den Hoed, Marcel, Duan, Qing, Engelter, Stefan T., Falcone, Guido J., Gottesman, Rebecca F., Grewal, Raji P., Gudnason, Vilmundur, Gustafsson, Stefan, Haessler, Jeffrey, Harris, Tamara B., Hassan, Ahamad, Havulinna, Aki S., Heckbert, Susan R., Holliday, Elizabeth G., Howard, George, Hsu, Fang-Chi, Hyacinth, Hyacinth I., Ikram, M. Arfan, Ingelsson, Erik, Irvin, Marguerite R., Jian, Xueqiu, Jimenez-Conde, Jordi, Johnson, Julie A., Jukema, J. Wouter, Kanai, Masahiro, Keene, Keith L., Kissela, Brett M., Kleindorfer, Dawn O., Kooperberg, Charles, 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., Psaty, Bruce M., Pulit, Sara L., Rannikmae, Kristiina, Reiner, Alexander P., Rexrode, Kathryn M., Rice, Kenneth, Rich, Stephen S., Ridker, Paul M., Rost, Natalia S., Rothwell, Peter M., Rotter, Jerome I., 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 L. M., Tanislav, Christian, Tatlisumak, Turgut, Taylor, Kent D., Thijs, Vincent N. S., Thorleifsson, Gudmar, Thorsteinsdottir, Unnur, Tiedt, Steffen, Trompet, Stella, Tzourio, Christophe, van Duijn, Cornelia M., Walters, Matthew, Wareham, Nicholas J., Wassertheil-Smoller, Sylvia, Wilson, James G., Wiggins, Kerri L., Yang, Qiong, Yusuf, Salim, Bis, Joshua C., Pastinen, Tomi, Ruusalepp, Arno, Schadt, Eric E., Koplev, Simon, Bjorkegren, Johan L. M., Codoni, Veronica, Civelek, Mete, Smith, Nicholas L., Tregouet, David A., Christophersen, Ingrid E., Roselli, Carolina, Lubitz, Steven A., Ellinor, Patrick T., Tai, E. Shyong, Kooner, Jaspal S., Kato, Norihiro, He, Jiang, van der Harst, Pim, Elliott, Paul, Chambers, John C., Takeuchi, Fumihiko, Johnson, Andrew D., Sanghera, Dharambir K., Melander, Olle, Jern, Christina, Strbian, Daniel, Fernandez-Cadenas, Israel, Longstreth, W. T., Jr., Rolfs, Arndt, Hata, Jun, Woo, Daniel, Rosand, Jonathan, Pare, Guillaume, Hopewell, Jemma C., Ingelsson, Martin, Saleheen, Danish, Stefansson, Kari, Worrall, Bradford B., Kittner, Steven J., Seshadri, Sudha, Fornage, Myriam, Lind, Lars, Markus, Hugh S., Howson, Joanna M. M., Kamatani, Yoichiro, Debette, Stephanie, and Dichgans, Martin

Abstract

Stroke has multiple etiologies, but the underlying genes and pathways are largely unknown. We conducted a multiancestry genome-wide-association meta-analysis in 521,612 individuals (67,162 cases and 454,450 controls) and discovered 22 new stroke risk loci, bringing the total to 32. We further found shared genetic variation with related vascular traits, including blood pressure, cardiac traits, and venous thromboembolism, at individual loci (n = 18), and using genetic risk scores and linkage-disequilibrium-score regression. Several loci exhibited distinct association and pleiotropy patterns for etiological stroke sub-types. Eleven new susceptibility loci indicate mechanisms not previously implicated in stroke pathophysiology, with prioritization of risk variants and genes accomplished through bioinformatics analyses using extensive functional datasets. Stroke risk loci were significantly enriched in drug targets for antithrombotic therapy.

Published
2018
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23. Rare Missense Functional Variants at COL4A1and COL4A2in Sporadic Intracerebral Hemorrhage

Author

Chung, Jaeyoon, Hamilton, Graham, Kim, Minsup, Marini, Sandro, Montgomery, Bailey, Henry, Jonathan, Cho, Art E., Brown, Devin L., Worrall, Bradford B., Meschia, James F., Silliman, Scott L., Selim, Magdy, Tirschwell, David L., Kidwell, Chelsea S., Kissela, Brett, Greenberg, Steven M., Viswanathan, Anand, Goldstein, Joshua N., Langefeld, Carl D., Rannikmae, Kristiina, Sudlow, Catherine L.M., Samarasekera, Neshika, Rodrigues, Mark, Al-Shahi Salman, Rustam, Prendergast, James G.D., Harris, Sarah E., Deary, Ian, Woo, Daniel, Rosand, Jonathan, Van Agtmael, Tom, and Anderson, Christopher D.

Published
2021
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24. Meta-analyses among 21,500 cases and 40,600 controls

Author

Rannikmae, Kristiina, Sivakumaran, Vhinoth, Millar, Henry, Malik, Rainer, Anderson, Christopher D., Chong, Mike, Dave, Tushar, Falcone, Guido J., Fernandez-Cadenas, Israel, Jimenez-Conde, Jordi, Lindgren, Arne, Montaner, Joan, O'Donnell, Martin, Paré, Guillaume, Radmanesh, Farid, Rost, Natalia S., Słowik, Agnieszka, Soderholm, Martin, Traylor, Matthew, Pulit, Sara L., Seshadri, Sudha, Worrall, Brad B., Woo, Daniel, Markus, Hugh S., Mitchell, Braxton D., Dichgans, Martin, Rosand, Jonathan, and Sudlow, Cathie L.M.

Published
2017

25. Genetic Variants in CETP Increase Risk of Intracerebral Hemorrhage

Author

Anderson, Christopher D., Falcone, Guido J., Phuah, Chia-Ling, Radmanesh, Farid, Bart Brouwers, H., Battey, Thomas W. K., Biffi, Alessandro, Peloso, Gina M., Liu, Dajiang J., Ayres, Alison M., Goldstein, Joshua N., Viswanathan, Anand, Greenberg, Steven M., Selim, Magdy, Meschia, James F., Brown, Devin L., Worrall, Bradford B., Silliman, Scott L., Tirschwell, David L., Flaherty, Matthew L., Kraft, Peter, Jagiella, Jeremiasz M., Schmidt, Helena, Hansen, Björn M., Jimenez-Conde, Jordi, Giralt-Steinhauer, Eva, Elosua, Roberto, Cuadrado-Godia, Elisa, Soriano, Carolina, Van Nieuwenhuizen, Koen M., Klijn, Catharina J.M., Rannikmae, Kristiina, Samarasekera, Neshika, Al-Shahi Salman, Rustam, Sudlow, Catherine L., Deary, Ian J., Morotti, Andrea, Pezzini, Alessandro, Pera, Joanna, Urbanik, Andrzej, Pichler, Alexander, Enzinger, Christian, Norrving, Bo, Montaner, Joan, Fernandez-Cadenas, Israel, Delgado, Pilar, Roquer, Jaume, Lindgren, Arne, Slowik, Agnieszka, and Schmidt, Reinhold

Subjects
lipids (amino acids, peptides, and proteins)
Abstract

Objective: In observational epidemiologic studies, higher plasma high‐density lipoprotein cholesterol (HDL‐C) has been associated with increased risk of intracerebral hemorrhage (ICH). DNA sequence variants that decrease cholesteryl ester transfer protein (CETP) gene activity increase plasma HDL‐C; as such, medicines that inhibit CETP and raise HDL‐C are in clinical development. Here, we test the hypothesis that CETP DNA sequence variants associated with higher HDL‐C also increase risk for ICH.Methods: We performed 2 candidate‐gene analyses of CETP. First, we tested individual CETP variants in a discovery cohort of 1,149 ICH cases and 1,238 controls from 3 studies, followed by replication in 1,625 cases and 1,845 controls from 5 studies. Second, we constructed a genetic risk score comprised of 7 independent variants at the CETP locus and tested this score for association with HDL‐C as well as ICH risk.Results: Twelve variants within CETP demonstrated nominal association with ICH, with the strongest association at the rs173539 locus (odds ratio [OR] = 1.25, standard error [SE] = 0.06, p = 6.0 × 10−4) with no heterogeneity across studies (I2 = 0%). This association was replicated in patients of European ancestry (p = 0.03). A genetic score of CETP variants found to increase HDL‐C by ∼2.85mg/dl in the Global Lipids Genetics Consortium was strongly associated with ICH risk (OR = 1.86, SE = 0.13, p = 1.39 × 10−6).Interpretation: Genetic variants in CETP associated with increased HDL‐C raise the risk of ICH. Given ongoing therapeutic development in CETP inhibition and other HDL‐raising strategies, further exploration of potential adverse cerebrovascular outcomes may be warranted.

Published
2016
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26. THUR 121 Identifying participants with parkinson’s disease in uk biobank

Author

Bush Kathryn, Rannikmae Kristiina, Wilkinson Timothy, Nolan John, Schnier Christian, Bennett Michael, Cheng Jingjie, and Sudlow Cathie

Subjects
medicine.medical_specialty, Parkinson's disease, business.industry, Medical record, Disease, medicine.disease, Biobank, Psychiatry and Mental health, Internal medicine, Cohort, medicine, Surgery, Neurology (clinical), Diagnosis code, Medical diagnosis, business, Cohort study
Abstract

BackgroundLinkage to routinely collected NHS data from primary, secondary care and death certificates enables identification of participants with Parkinson’s Disease (PD) within the UK Biobank cohort of 5 00 000 adults. Validation of the accuracy of this data is required prior to their use in research studies.MethodIn this validation study participants (n=125) with a code indicating PD were identified from a sample of 17 000 participants in the cohort. Diagnoses were validated by expert adjudicators, based on free text electronic medical records. Positive predictive values (PPV,% of cases identified that are true cases) were calculated.ResultsPrimary care diagnostic codes identified 93% of PD cases, with a PPV of 95%. Combined secondary care and death data identified 42% of PD cases with a PPV of 84%.Combining diagnostic and medication codes identified more participants, but did not increase the PPV.ConclusionsThis study suggests that linkage to routinely collected healthcare data is a reliable method for identifying participants with PD in the UK Biobank cohort.Primary care diagnostic codes identified the highest proportion of participants and had the highest PPV, demonstrating the value of using primary care data to identify cases of disease in large population based cohort studies.

Published
2018
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27. GISCOME – Genetics of Ischaemic Stroke Functional Outcome network: A protocol for an international multicentre genetic association study

Author

Maguire, Jane M, primary, Bevan, Steve, additional, Stanne, Tara M, additional, Lorenzen, Erik, additional, Fernandez-Cadenas, Israel, additional, Hankey, Graeme J, additional, Jimenez-Conde, Jordi, additional, Jood, Katarina, additional, Lee, Jin-Moo, additional, Lemmens, Robin, additional, Levi, Christopher, additional, Norrving, Bo, additional, Rannikmae, Kristiina, additional, Rost, Natalia, additional, Rosand, Jonathan, additional, Rothwell, Peter M, additional, Scott, Rodney, additional, Strbian, Daniel, additional, Sturm, Jonathan, additional, Sudlow, Cathie, additional, Traylor, Matthew, additional, Thijs, Vincent, additional, Tatlisumak, Turgut, additional, Wieloch, Tadeusz, additional, Woo, Daniel, additional, Worrall, Bradford B, additional, Jern, Christina, additional, and Lindgren, Arne, additional

Published
2017
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28. Genetic variants in CETP increase risk of intracerebral hemorrhage

Author

Opleiding Neurochirurgie, Opleiding Neurologie, Brain, ZL Cerebrovasculaire Ziekten Medisch, Circulatory Health, Anderson, Christopher D., Falcone, Guido J., Phuah, Chia Ling, Radmanesh, Farid, Brouwers, H. Bart, Battey, Thomas W K, Biffi, Alessandro, Peloso, Gina M., Liu, Dajiang J., Ayres, Alison M., Goldstein, Joshua N., Viswanathan, Anand, Greenberg, Steven M., Selim, Magdy, Meschia, James F., Brown, Devin L., Worrall, Bradford B., Silliman, Scott L., Tirschwell, David L., Flaherty, Matthew L., Kraft, Peter, Jagiella, Jeremiasz M., Schmidt, Helena, Hansen, Björn M., Jimenez-Conde, Jordi, Giralt-Steinhauer, Eva, Elosua, Roberto, Cuadrado-Godia, Elisa, Soriano, Carolina, van Nieuwenhuizen, Koen M., Klijn, Catharina J M, Rannikmae, Kristiina, Samarasekera, Neshika, Salman, Rustam Al Shahi, Sudlow, Catherine L., Deary, Ian J., Morotti, Andrea, Pezzini, Alessandro, Pera, Joanna, Urbanik, Andrzej, Pichler, Alexander, Enzinger, Christian, Norrving, Bo, Montaner, Joan, Fernandez-Cadenas, Israel, Delgado, Pilar, Roquer, Jaume, Lindgren, Arne, Slowik, Agnieszka, Schmidt, Reinhold, Kidwell, Chelsea S., Kittner, Steven J., Waddy, Salina P., Langefeld, Carl D., Abecasis, Goncalo, Willer, Cristen J., Kathiresan, Sekar, Woo, Daniel, Rosand, Jonathan, Opleiding Neurochirurgie, Opleiding Neurologie, Brain, ZL Cerebrovasculaire Ziekten Medisch, Circulatory Health, Anderson, Christopher D., Falcone, Guido J., Phuah, Chia Ling, Radmanesh, Farid, Brouwers, H. Bart, Battey, Thomas W K, Biffi, Alessandro, Peloso, Gina M., Liu, Dajiang J., Ayres, Alison M., Goldstein, Joshua N., Viswanathan, Anand, Greenberg, Steven M., Selim, Magdy, Meschia, James F., Brown, Devin L., Worrall, Bradford B., Silliman, Scott L., Tirschwell, David L., Flaherty, Matthew L., Kraft, Peter, Jagiella, Jeremiasz M., Schmidt, Helena, Hansen, Björn M., Jimenez-Conde, Jordi, Giralt-Steinhauer, Eva, Elosua, Roberto, Cuadrado-Godia, Elisa, Soriano, Carolina, van Nieuwenhuizen, Koen M., Klijn, Catharina J M, Rannikmae, Kristiina, Samarasekera, Neshika, Salman, Rustam Al Shahi, Sudlow, Catherine L., Deary, Ian J., Morotti, Andrea, Pezzini, Alessandro, Pera, Joanna, Urbanik, Andrzej, Pichler, Alexander, Enzinger, Christian, Norrving, Bo, Montaner, Joan, Fernandez-Cadenas, Israel, Delgado, Pilar, Roquer, Jaume, Lindgren, Arne, Slowik, Agnieszka, Schmidt, Reinhold, Kidwell, Chelsea S., Kittner, Steven J., Waddy, Salina P., Langefeld, Carl D., Abecasis, Goncalo, Willer, Cristen J., Kathiresan, Sekar, Woo, Daniel, and Rosand, Jonathan

Published
2016

29. Abstract 11: The Utility of Causative Classification System: Correlation between Causative and Phenotypic Stroke Subtypes

Author

Arsava, Ethem Murat, primary, Barrett, Kevin, additional, Biffi, Alessandro, additional, Brenner, David, additional, Brown, Robert, additional, Gamble, Dale, additional, Grazer, Anja, additional, Gschwendtner, Andreas, additional, Helenius, Johanna, additional, Huq, Mohammed, additional, Katschnig, Petra, additional, Katsnelson, Michael, additional, Kittner, Steven, additional, Li, Linxin, additional, Labovitz, Daniel L, additional, Malik, Shaneela, additional, Meschia, James, additional, Ossi, Raid, additional, Peddareddygari, Leema, additional, Pucek, Mateusz, additional, Rannikmae, Kristiina, additional, Rhodes, David, additional, Saraf, Neha, additional, Sheikh, Huma, additional, Stoegerer, Eva, additional, Southerland, Andrew, additional, Weissman, Darren, additional, Woo, Daniel, additional, Worrall, Bradford, additional, and Ay, Hakan, additional

Published
2012
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30. Shared genetic basis for migraine and ischemic stroke: A genome-wide analysis of common variants.

Author

Malik, Rainer, Freilinger, Tobias, Winsvold, Bendik S, Anttila, Verneri, Vander Heiden, Jason, Traylor, Matthew, de Vries, Boukje, Holliday, Elizabeth G, Terwindt, Gisela M, Sturm, Jonathan, Bis, Joshua C, Hopewell, Jemma C, Ferrari, Michel D, Rannikmae, Kristiina, Wessman, Maija, Kallela, Mikko, Kubisch, Christian, Fornage, Myriam, Meschia, James F, and Lehtimäki, Terho

Published
2015
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31. Abstract 154: Sex-specific Genome Wide Association Study Of Early-onset Ischemic Stroke

Author

Tomppo, Liisa, Rannikmae, Kristiina, Stanne, Tara M, Putaala, Jukka, Strbian, Daniel, Jern, Christina, de Leeuw, Frank-Erik, Cadenas, Israel Fernandez, Slowik, Agnieszka M, Boncoraglio, Giorgio, Lindgren, Arne, Conde, Jordi J, Schmidt, Reinhold, Sharma, Pankaj, Lemmens, Robin, MELANDER, Olle, Rothwell, Peter, Levi, Christopher, Sudlow, Catherine, Debette, Stephanie, Metso, Tiina, Pare, Guillaume, Markus, Hugh, Saleheen, Danish, Danesh, John, Zand, Ramin, Worrall, Bradford B, Meschia, James F, Rundek, Tatjana, Woo, Daniel, Lee, Jin-moo, Irvin, Marguerite R, McDonough, Caitrin W, Rexrode, Kathryn M, Wassertheil-smoller, Sylvia W, Rosand, Jonathan, Gieger, Christian, Muller-Nurasyid, Martina, Salomaa, Veikko V, Kamatani, Yoichiro, Walters, Robin, Chen, Zhengming, Dichgans, Martin, Malik, Rainer, Gaynor, Brady, Cole, John, Xu, Huichun, Mitchell, Braxton D, and Kittner, Steven J

Abstract

Introduction:Genetic studies of early-onset disease have been an effective strategy to identify novel pathways and drug targets generalizable also to later-onset disease. Few studies have investigated the sex-specific genetic associations with early-onset ischemic stroke even though several features of ischemic stroke differ between males and females. We hypothesized that stratifying the GWAS by sex would reveal novel stroke loci.Methods:We performed a transethnic ischemic stroke GWAS of 3,056 female cases and 4,462 male cases < 60 years-old and 16,192 and 16,048 sex-matched controls, respectively, from the Early Onset Stroke Genetics Consortium.Results:We identified a significant association in women with a locus in close proximity to TMX1, a transmembrane platelet protein that inhibits platelet function. Additionally, we identified 2 other suggestive (P < 5 x 10-6) loci in females (see Table), i.e., at APOH, which encodes beta2-glycoprotein I, an established GWAS locus for lipoprotein(a), and LRFN2which has been previously reported to associate with obesity-related measures and type II diabetes. We observed suggestive evidence for association in males with MMP3/MMP12, a known stroke susceptibility locus.Conclusions:Despite a very modest sample size, sex-specific analyses identified suggestive associations at biologically important novel loci in females and a known stroke locus in males. Further studies of sex-specific associations in both early- and later-onset ischemic stroke are needed.

Published
2022
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32. Abstract P368: Developing Automated Methods for Disease Subtyping in UK Biobank: An Exemplar Study on Stroke

Author

Rannikmae, Kristiina, Wu, Honghan, Tominey, Steven, Whiteley, William, Allen, Naomi, and Sudlow, Cathie L

Abstract

Objective:In UK Biobank (UKB), a large population-based prospective study, cases of many diseases are ascertained through linkage to routinely collected, coded national health datasets. However routinely collected coded data cannot always provide sufficient accuracy or granularity (i.e. sub-phenotypes) for research studies. For example, while ischemic stroke codes appear accurate, the precision for hemorrhagic stroke codes (intracerebral hemorrhage [ICH] and subarachnoid hemorrhage [SAH]) may be as poor as <50%. We investigated whether automated analysis of radiology reports could improve disease subtyping in UKB, using stroke as an exemplar disease.Methods:From a sub-population of 17,249 UKB participants, we ascertained those with an incident stroke code and ≥1 clinical brain scan report. We used automated methods (a combination of natural language processing and clinical knowledge inference) on brain scan reports to assign a stroke subtype (ischemic vs ICH vs SAH) for each participant and assessed performance by precision (positive predictive value) and recall (sensitivity) at both entity and patient levels.Results:Of 225 participants with an incident stroke code, 207 had a relevant brain scan report. Entity level precision and recall ranged from 78% to 100%. Automated methods showed precision (positive predictive value) and recall (sensitivity) at patient level that were very good for ICH (both 89%), good for SAH (both 82%), but, as expected, lower for ischemic stroke (73%, and 64%, respectively), suggesting coded data remains the preferred method for identifying the latter stroke subtype (Table 1).Discussion:Future research should validate these findings in another dataset.Conclusion:Our novel automated method applied to radiology reports provides a feasible, scalable and accurate solution to improve disease subtyping when used in conjunction with administrative coded health data.

Published
2021
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33. Abstract 154: Genetic Variants in CETP That Increase HDL Levels also Increase Risk of Intracerebral Hemorrhage.

Author

Falcone, Guido J, Phuah, Chia-Ling, Radmanesh, Farid, Peloso, Gina M, Meschia, James F, Selim, Magdy, Brown, Devin L, Worrall, Bradford B, Silliman, Scott L, Tirschwell, David L, Jimenez-Conde, Jordi, Klijn, Catharina J, Sudlow, Catherine L, Rannikmae, Kristiina, Pezzini, Alessandro, Norrving, Bo, Montaner, Joan, Lindgren, Arne, Slowik, Agnieszka, and Kidwell, Chelsea S

Published
2017
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