Author: "Hopewell, Jemma C." / Publisher: lippincott williams & wilkins - Searchworks@Jio Institute Digital Library Search Results

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28 results on '"Hopewell, Jemma C."'

1. Apolipoprotein Proteomics for Residual Lipid-Related Risk in Coronary Heart Disease.

Author: Clarke, Robert, Von Ende, Adam, Schmidt, Lukas E., Xiaoke Yin, Hill, Michael, Hughes, Alun D., Pechlaner, Raimund, Willeit, Johann, Kiechl, Stefan, Watkins, Hugh, Theofilatos, Konstantinos, Hopewell, Jemma C., and Mayr, Manuel
Published: 2023
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2. Determining the Relationship Between Blood Pressure, Kidney Function, and Chronic Kidney Disease: Insights From Genetic Epidemiology.

Author: Staplin, Natalie, Herrington, William G., Murgia, Federico, Ibrahim, Maysson, Bull, Katherine R., Judge, Parminder K., Ng, Sarah Y.A., Turner, Michael, Zhu, Doreen, Emberson, Jonathan, Landray, Martin J., Baigent, Colin, Haynes, Richard, Hopewell, Jemma C., and Judge, Parminder
Abstract: Background: It is well established that decreased kidney function can increase blood pressure (BP), but it is unproven whether moderately elevated BP causes chronic kidney disease (CKD) or glomerular hyperfiltration.Methods: 311 119 White British UK Biobank participants were included in logistic regression analyses to estimate the odds of CKD (defined as long-term kidney replacement therapy, estimated glomerular filtration rate [eGFR]< 60mL/min/1.73m2, or urinary albumin:creatinine ratio ≥3 mg/mmol) associated with higher genetically predicted BP using genetic risk scores comprising 219 systolic and 223 diastolic BP loci. Analyses estimating associations with clinical categories of eGFR and urinary albumin:creatinine ratio were also conducted, with an eGFR ≥120 mL (min·1.73m2) considered evidence of glomerular hyperfiltration.Results: 21 623 participants had CKD: 7781 with reduced eGFR and 15 500 with albuminuria. 1828 participants had an eGFR ≥120 mL/min/1.73m2. Each genetically predicted 10 mmHg higher systolic BP and 5 mmHg higher diastolic BP were associated with a 37% (95% CI, 1.29-1.45) and 19% (1.14-1.25) higher odds of CKD, respectively. Associations were evident for both the reduced eGFR and albuminuria components of the CKD outcome. The odds of hyperfiltration (versus an eGFR ≥60 and <90 mL/min/1.73m2 were 49% higher (95% CI, 1.21-1.84) for each genetically predicted 10 mmHg higher systolic BP. Associations with CKD and hyperfiltration were similar irrespective of preexisting diabetes, vascular disease, or different levels of adiposity.Conclusions: In this general population, genetic epidemiological evidence supports a causal role of life-long differences in BP for decreased kidney function, glomerular hyperfiltration, and albuminuria. Physiological autoregulation may not afford complete renal protection against the moderate BP elevations. [ABSTRACT FROM AUTHOR]
Published: 2022
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3. 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

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

Author: Chauhan, Ganesh, Adams, Hieab H H, Jian, Xueqiu, Sharma, Pankaj, Sudlow, Cathie L M, Rosand, Jonathan, Woo, Daniel, Cole, John W, Meschia, James F, Slowik, Agnieszka, Thijs, Vincent, Lindgren, Arne, Melander, Olle, Malik, Rainer, 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, Traylor, Matthew, 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, Pulit, Sara L, 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, Amouyel, Philippe, Worrall, Bradford B, Dichgans, Martin, Kittner, Steven J, Markus, Hugh S, Ikram, Mohammad A, Fornage, Myriam, Launer, Lenore J, Seshadri, Sudha, Longstreth, W. T., Debette, Stéphanie, Mazoyer, Bernard, Network, Stroke Genetics, Almgren, Peter, Anderson, Christopher D, Attia, John, Ay, Hakan, Brown, Robert D, Bustamante, Mariana, Zhu, Yi-Cheng, Cheng, Yu-Ching, Cotlarciuc, Ioana, Cruchaga, Carlos, de Bakker, Paul Iw, Delavaran, Hossein, Engström, Gunnar, Kaffashian, Sara, Heitsch, Laura, Holliday, Elizabeth, Ibanez, Laure, Ilinca, Andreea, Irvin, Marguerite R, Jackson, Rebecca D, Jimenez-Conde, Jordi, Jood, Katarina, Schilling, Sabrina, Kissela, Brett M, Kleindorfer, Dawn O, Labovitz, Daniel, Laurie, Cathy C, Lemmens, Robin, Levi, Christopher, Li, Linxin, Lindgren, Arne G, Beecham, Gary W, Maguire, Jane, Müller-Nurasyid, Martina, Norrving, Bo, Peddareddygari, Leema Reddy, Pera, Joanna, Satizabal, Claudia L, Montine, Thomas J, Rexrode, Kathryn, Ribasés, Marta, Roquer, Jaume, Rost, Natalia S, Sacco, Ralph L, Schmidt, Reinhold, Schellenberg, Gerard D, Soriano-Tárraga, Carolina, Stanne, Tara, Stauch, Konstantin, Stine, O. C., Sudlow, Cathie Lm, Thijs, Vincent N S, Weir, David, Williams, Stephen R, Kjartansson, Olafur, Xu, Huichun, Hyacinth, Hyacinth I, Marini, Sandro, Nyquist, Paul, Lewis, Cathryn, Hansen, Bjorn, Guðnason, Vilmundur, Biffi, Alessandro, Kourkoulis, Christina, Anderson, Chris, Giese, Anne-Katrin, Sacco, Ralph, Chung, Jong-Won, Kim, Gyeong-Moon, Knopman, David S, Lubitz, Steven, Bourcier, Romain, Howson, Joanna, Granata, Alessandra, Drazyk, Anna, Markus, Hugh, Wardlaw, Joanna, Mitchell, Braxton, Cole, John, Hopewell, Jemma, Griswold, Michael E, Walters, Robin, Turnbull, Iain, Worrall, Bradford, Bis, Josh, Reiner, Alex, Dhar, Raj, Prasad, Kameshwar, Sarnowski, Chloé, Windham, B Gwen, Aparicio, Hugo Javier, Yang, Qiong, Chasman, Daniel, Phuah, Chia-Ling, Liu, Guiyou, Elkind, Mitchell, Lange, Leslie, Rost, Natalia, James, Michael, Gottesman, Rebecca F, Stewart, Jill, Vojinovic, Dina, Parati, Eugenio, Boncoraglio, Giorgio, Zand, Ramin, Bijlenga, Philippe, Selim, Magdy, Grond-Ginsbach, Caspar, Strbian, Daniel, Mosley, Thomas H, Tomppo, Liisa, Sallinen, Hanne, Pfeiffer, Dorothea, Torres, Nuria, Barboza, Miguel, Laarman, Melanie, Carriero, Roberta, Soriano, Carolina, Gill, Dipender, Debette, Stephanie, Mishra, Aniket, Wu, Jer-Yuarn, Ko, Tai-Ming, Bione, Silvia, Tatlisumak, Turgut, Holmegaard, Lukas, Yue, Suo, Bis, Joshua C, Saba, Yasaman, Bersano, Anna, Schlicht, Kristina, Ninomiya, Toshiharu, Oberstein, Saskia Lesnik, Lee, Tsong-Hai, Schmidt, Helena, Wasselius, Johan, Drake, Mattias, Stenman, Martin, Crawford, Katherine, Lena, Umme, Mateen, Farrah, Takeuchi, Fumihiko, Wu, Ona, Schirmer, Markus, Cramer, Steve, Golland, Polina, Brown, Robert, Meschia, James, Ross, Owen A, Pare, Guillaume, Chong, Mike, Yamaguchi, Shuhei, Gwinn, Katrina, Chen, Christopher, Koenig, Jim, Giralt, Eva, Saleheen, Danish, de Leeuw, Frank-Erik, Klijn, Karin, Kamatani, Yoichiro, Kubo, Michiaki, Nabika, Toru, Okada, Yukinori, Pedersen, Annie, Olsson, Maja, Martín, Juan José, Tan, Eng King, Frid, Petrea, Lee, Chaeyoung, Tregouet, David, Leung, Thomas, Kato, Norihiro, Choy, Richard, Loo, Keat Wei, Rinkel, Gabriel, Franca, Paulo, Cendes, Iscia, Carrera, Caty, Fernandez-Cadenas, Israel, Montaner, Joan, Kim, Helen, Rajan, Kumar B, Owolabi, Mayowa, Sofat, Reecha, Bakker, Mark, Ruigrok, Ynte, Hauer, Allard, van der Laan, Sander W, Irvin, Ryan, Sargurupremraj, Murali, Pezzini, Alessandro, Aggarwal, Neelum T, Abd-Allah, Foad, Liebeskind, David, Tan, Rhea, Danesh, John, Donatti, Amanda, Avelar, Wagner, Broderick, Joseph, Sudlow, Cathie, De Jager, Philip L, Rannikmae, Kristiina, McDonough, Caitrin Wheeler, van Agtmael, Tom, Walters, Matthew, Söderholm, Martin, Lorentzen, Erik, Olsson, Sandra, Olsson, Martina, Akinyemi, Rufus, Evans, Denis A, Cotlatciuc, Ioana, McArdle, Patrick, Dave, Tushar, Kittner, Steven, Faber, James E, Millwood, Iona, Márquez, Elsa Valdés, Mancuso, Michelangelo, Vibo, Riina, Teumer, Alexander, Psaty, Bruce M, Korv, Janika, Majersik, Jennifer, DeHavenon, Adam, Alexander, Matthew, Sale, Michele, Southerland, Andrew, Owens, Debra, Psaty, Bruce, Rotter, Jerome I, Wolfe, Stacey Quintero, Langefeld, Carl, Konrad, Jan, Sheth, Kevin, Falcone, Guido, Donahue, Kathleen, Simpkins, Alexis N, Liang Byorn, Tan Wei, Rice, Kenneth, Chan, Bernard, Clatworthy, Phil, Florez, Jose, Harshfield, Eric, Hozawa, Atsushi, Hsu, Chung, Hu, Chaur-Jong, Ihara, Masafumi, Lange, Marcos, Lopez, Oscar L, Lee, Soo Ji, Lee, I-Hui, Musolino, Patricia, Nakatomi, Hirofumi, Park, Kwang-Yeol, Riley, Chris, Sung, Joohon, Suzuki, Hideaki, Vo, Katie, Liao, Jiemin, Washida, Kazuo, Ibenez, Laura Garcia, Hofman, Albert, Algra, Ale, Reiner, Alex P, Doney, Alexander S F, Gschwendtner, Andreas, Vicente, Astrid M, Nordestgaard, Børge G, Carty, Cara L, Cheng, Ching-Yu, Palmer, Colin N A, Gamble, Dale M, Ringelstein, E Bernd, Valdimarsson, Einar, Davies, Gail, Wong, Tien Y, Pasterkamp, Gerard, Kuhlenbäumer, Gregor, Thorleifsson, Gudmar, Falcone, Guido J, Pare, Guillame, Ikram, Mohammad K, Aparicio, Hugo J, Deary, Ian, Hopewell, Jemma C, Liu, Jingmin, van der Lee, Sven J, Attia, John R, Ferro, Jose M, Bis, Joshua, Furie, Karen, Stefansson, Kari, Berger, Klaus, Kostulas, Konstantinos, Rannikmae, Kristina, Ikram, M Arfan, Sargurupremraj, Muralidharan, Amin, Najaf, Benn, Marianne, Farrall, Martin, Pandolfo, Massimo, Nalls, Mike, van Zuydam, Natalie R, Chouraki, Vincent, Abrantes, Patricia, Higgins, Peter, Lichtner, Peter, DeStefano, Anita L, Clarke, Robert, Abboud, Sherine, Oliveira, Sofia A, Gretarsdottir, Solveig, Mosley, Thomas, Battey, Thomas Wk, Thorsteinsdottir, Unnur, Thijs, Vincent Ns, Zhao, Wei, Chen, Wei-Min, Romero, Jose R, 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, Maillard, Pauline, Barral, Sandra, Beach, Thomas G, Becker, James T, Beekly, Duane, Bennett, David A, Bigio, Eileen H, Bird, Thomas D, Blacker, Deborah, Boeve, Bradley F, DeCarli, Charles, 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, Wardlaw, Joanna M, Carney, Regina M, Carrasquillo, Minerva M, Carroll, Steven L, Chui, Helena C, Clark, David G, Cribbs, David H, Crocco, Elizabeth A, Hernández, Maria Del C Valdés, Demirci, F Yesim, Dick, Malcolm, Dickson, Dennis W, Duara, Ranjan, Ertekin-Taner, Nilufer, Faber, Kelley M, Fallin, M Daniele, Fallon, Kenneth B, Fardo, David W, Luciano, Michelle, 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, Hofer, Edith, Liewald, David, 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, Deary, Ian J, 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, Starr, John M, 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, Bastin, Mark E, Lang-Walker, Rosalyn, Larson, Eric B, Leverenz, James B, Levey, Allan I, Li, Ge, Lieberman, Andrew P, Logue, Mark W, Lunetta, Kathryn L, Lyketsos, Constantine G, Muñoz Maniega, Susana, 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, Slagboom, P Eline, Miller, Bruce L, Miller, Carol A, Miller, Joshua W, Morris, John C, Murrell, Jill R, Naj, Adam C, Obisesan, Thomas O, Olichney, John M, Pankratz, Vernon S, Beekman, Marian, 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, Deelen, Joris, 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, Uh, Hae-Won, Rosenberg, Roger N, Sager, Mark A, Sano, Mary, Saykin, Andrew J, 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, Trompet, Stella, Brodaty, Henry, 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, Wright, Margaret J, Woltjer, Randall L, Wright, Clinton B, Younkin, Steven G, Yu, Chang-En, Yu, Lei, Chu, Audrey Y, Havulinna, Aki S, Ames, David, Smith, Albert Vernon, Choi, Seung Hoan, Garcia, Melissa E, Manichaikul, Ani, Gustafsson, Stefan, Bartz, Traci M, Boncoraglio, Giorgio B, Bellenguez, Céline, Vidal, Jean Sebastien, Wiggins, Kerri L, Xue, Flora, Ripatti, Samuli, Liu, Yongmei, Hoed, Marcel den, Heckbert, Susan R, Smith, Nicholas L, Buring, Julie E, Ridker, Paul M, Berr, Claudine, Dartigues, Jean-François, Beecham, Ashley H, Hamsten, Anders, Magnusson, Patrik K, Pedersen, Nancy L, Lannfelt, Lars, Lind, Lars, Lindgren, Cecilia M, Morris, Andrew P, Koudstaal, Peter J, Portegies, Marileen Lp, Blanton, Susan H, Uitterlinden, André G, de Craen, Anton Jm, Ford, Ian, Jukema, J Wouter, Stott, David J, Allen, Norrina B, Sale, Michele M, Johnson, Andrew D, White, Charles C, Paulista Markus, Marcello Ricardo, Nalls, Michael A, Beiser, Alexa, Vartiainen, Erkki, French, Curtis R, Kurth, Tobias, Harris, Tamara B, deStefano, Anita L, Schmidt, Carsten Oliver, Salomaa, Veikko, Wen, Wei, Ingelsson, Erik, Chasman, Daniel I, Verhaaren, Benjamin F J, Hilal, Saima, Thalamuthu, Anbupalam, Smith, Jennifer A, Ikram, M Kamran, Adams, Hieab H, Lopez, Lorna M, van Buchem, Mark A, Armstrong, Nicola J, van der Grond, Jeroen, Smith, Albert V, Hegenscheid, Katrin, de Andrade, Mariza, Atkinson, Elizabeth J, Beiser, Alexa S, Boerwinkle, Eric, Chong, Elizabeth, Brickman, Adam M, Bryan, R Nick, Chen, Christopher P L H, de Craen, Anton J M, Crivello, Fabrice, Schofield, Peter R, Dufouil, Carole, Elkind, Mitchell S V, Freudenberger, Paul, Habes, Mohamad, Heiss, Gerardo, Kwok, John B, Ibrahim-Verbaas, Carla A, Lewis, Cora E, Liewald, David C M, van der Lugt, Aad, Martinez, Oliver O, Nauck, Matthias, Niessen, Wiro J, Oostra, Ben A, Rice, Kenneth M, von Sarnowski, Bettina, Schreiner, Pamela J, Schuur, Maaike, Sidney, Stephen S, Sigurdsson, Sigurdur, Stott, David J M, van Swieten, John C, Töglhofer, Anna Maria, Turner, Stephen T, Vernooij, Meike W, Wang, Jing J, Wolf, Christiane, Zijdenbos, Alex, Kardia, Sharon L R, DeCarli, Charles C, Seshadri, Sudha S, Kavousi, Maryam, Franceschini, Nora, Isaacs, Aaron, Abecasis, Gonçalo R, Schminke, Ulf, Post, Wendy, Cupples, L Adrienne, Huffman, Jennifer E, Lehtimäki, Terho, Baumert, Jens, Münzel, Thomas, Dehghan, Abbas, North, Kari, Oostra, Ben, Stoegerer, Eva-Maria, Hayward, Caroline, Raitakari, Olli, Meisinger, Christa, Schillert, Arne, Sanna, Serena, Völzke, Henry, Thorsson, Bolli, Fox, Caroline S, Wittfeld, Katharina, Rivadeneira, Fernando, Nambi, Vijay, Halperin, Eran, Petrovic, Katja E, Peltonen, Leena, Wichmann, H Erich, Schnabel, Renate B, Dörr, Marcus, Parsa, Afshin, Aspelund, Thor, Grabe, Hans J, Demissie, Serkalem, Kathiresan, Sekar, Reilly, Muredach P, Taylor, Kent, Uitterlinden, Andre, Couper, David J, Sitzer, Matthias, Kähönen, Mika, Illig, Thomas, Wild, Philipp S, Hosten, Norbert, Orru, Marco, Lüdemann, Jan, Shuldiner, Alan R, Eiriksdottir, Gudny, Seissler, Jochen, Zeller, Tanja, Usala, Gianluca, Ernst, Florian, D'Agostino, Ralph B, O'Leary, Daniel H, Ballantyne, Christie, Thiery, Joachim, Ziegler, Andreas, Lakatta, Edward G, Chilukoti, Ravi Kumar, Völker, Uwe, Wolf, Philip A, Polak, Joseph F, Li, Xia, Rathmann, Wolfgang, Uda, Manuela, Klopp, Norman, Wilson, James F, Viikari, Jorma, Koenig, Wolfgang, Blankenberg, Stefan, Newman, Anne B, Witteman, Jacqueline, van Duijn, Cornelia, Scuteri, Angelo, Homuth, Georg, Gudnason, Vilmundur, O'Donnell, Christopher J, Bordeaux population health (BPH), 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), Lund University [Lund], Stroke Genetics Network (SiGN), METASTROKE, Alzheimer’s Disease Genetics Consortium (ADGC), Neurology Working Group of the Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) Consortium, Peter Almgren, MSC, Christopher D. Anderson, MD, Donna K. Arnett, PhD, MSPH, John Attia, MD, PhD, FRACP, FRCPC, Hakan Ay, MD, Oscar R. Benavente, MD, Steve Bevan, PhD, Robert D. Brown, MD, Mariana Bustamante, PhD, Yu-Ching Cheng, PhD, John W. Cole, MD, MS, Ioana Cotlarciuc, PhD, Carlos Cruchaga, PhD, Paul IW. de Bakker, PhD, Hossein Delavaran, MD, PhD, Martin Dichgans, MD, Gunnar Engström, MD, PHD, PROF, Myriam Fornage, PhD, Raji P. Grewal, MD, Laura Heitsch, MD, Elizabeth Holliday, MSc, PhD, Laure Ibanez, PhD, Andreea Ilinca, MD, Marguerite R. Irvin, PhD, Rebecca D. Jackson, MD, Christina Jern, MD, PhD, Jordi Jimenez-Conde, MD, PhD, Julie A. Johnson, PharmD, Katarina Jood, MD, PhD, Brett M. Kissela, MD, MS, Steven J. Kittner, MD, Dawn O. Kleindorfer, MD, MS, Daniel Labovitz, MD, Cathy C. Laurie, PhD, Jin-Moo Lee, MD, PhD, Robin Lemmens, MD PhD, Christopher Levi, MBBS B Med Sci FRACP, Linxin Li, DPhil, Arne G. Lindgren, MD, PhD, Jane Maguire, PhD, Hugh S. Markus, FRCP, Patrick F. McArdle, PhD, Olle Melander, MD, PHD, PROF, James F. Meschia, MD, Braxton D. Mitchell, PhD, Martina Müller-Nurasyid, PhD, Bo Norrving, MD, PhD, Leema Reddy Peddareddygari, MD, Joanna Pera, MD, PhD, Sara L. Pulit, PhD, Kathryn Rexrode, MD, MPH, Marta Ribasés, PhD, BSc, Jaume Roquer, MD, PhD, Natalia S. Rost, MD, Peter M. Rothwell, FMedSci, Tatjana Rundek, MD PhD, Ralph L. Sacco, MD MS, Reinhold Schmidt, MD, Pankaj Sharma, MD PhD, Agnieszka Slowik, MD, PhD, Carolina Soriano-Tárraga, BSc, PhD, Tara Stanne, PhD, Konstantin Stauch, PhD, O C. Stine, PhD, Cathie LM. Sudlow, BMBCh, MSc, DPhil, FRCP (Ed), Vincent N.S. Thijs, MD, PhD, Sylvia Wasssertheil-Smoller, PhD, David Weir, PhD, Stephen R. Williams, PhD, Quenna Wong, PhD, Daniel Woo, MD, MS, Bradford B. Worrall, MD, MSc, Huichun Xu, MD, PhD, Sudha Seshadri, MD, Hyacinth I Hyacinth, MD, Sandro Marini, MD, Paul Nyquist, MD, PhD, Cathryn Lewis, PhD, Bjorn Hansen, MD, Bo Norrving, MD, PhD, Jonathan Rosand, MD, Alessandro Biffi, MD, Christina Kourkoulis, Bachelor, Chris Anderson, MD, MMSc, Anne-Katrin Giese, MD, Ralph Sacco, MD, MS, Pankaj Sharma, MD, PhD, Jong-Won Chung, MD, MSc, Gyeong-Moon Kim, MD, Steven Lubitz, MD, MPH, Romain Bourcier, MD, Joanna Howson, PhD, Alessandra Granata, PhD, Anna Drazyk, MRCPI, Hugh Markus, MD, Joanna Wardlaw, MD, Braxton Mitchell, MPH, PHD, John Cole, MD, MS, Jemma Hopewell, PhD, FESC, Robin Walters, MA, PhD, PgDip, Iain Turnbull, BA(Hons) MB BChir MRCP(UK) MRCGP, Bradford Worrall, MD, MSc, Josh Bis, PhD, Alex Reiner, MD, MSc, Raj Dhar, MD, Laura Heitsch, MD, Jin-Moo Lee, MD, PhD, Kameshwar Prasad, MD, DM, MMSc, FRCP(Edin), FAMS, Chloé Sarnowski, PhD, Hugo Javier Aparicio, MD, Qiong Yang, PhD, Daniel Chasman, PhD, Kathryn Rexrode, MD, MPH, Chia-Ling Phuah, MD, Guiyou Liu, PhD, Mitchell Elkind, MD, MSc, Leslie Lange, PhD, Natalia Rost, MD, Michael James, MD, Jill Stewart, PhD, Dina Vojinovic, MD, MS, Vincent Thijs, MD, PhD, Eugenio Parati, MD, Giorgio Boncoraglio, MD, Ramin Zand, MD, Philippe Bijlenga, MD, PhD, Magdy Selim, MD, PhD, Caspar Grond-Ginsbach, PhD, Daniel Strbian, MD, PhD, Liisa Tomppo, MD, Hanne Sallinen, MD, Dorothea Pfeiffer, MD, Nuria Torres, MSc, Miguel Barboza, MD, Melanie Laarman, PhD candidate, Roberta Carriero, PhD, Elizabeth Holliday, PhD, Jordi Jimenez-Conde, MD, PhD, Carolina Soriano, BSc, PhD, Dipender Gill, PhD, Stephanie Debette, MD, PhD, Aniket Mishra, PhD, Jer-Yuarn Wu, PhD, Tai-Ming Ko, PhD, Silvia Bione, PhD, Katarina Jood, MD, PhD, Turgut Tatlisumak, MD, PhD, Lukas Holmegaard, PhD, Suo Yue, system engineer, Anna bersano, MD, PhD, Joanna Pera, MD, PhD, Agnieszka Slowik, MD, PhD, Christopher Levi, MBBS B Med Sci FRACP, Kristina Schlicht, Dipl. Biol., Robin Lemmens, MD, PhD, Toshiharu Ninomiya, MD, PhD, Saskia Lesnik Oberstein, PhD, Tsong-Hai Lee, MD, PhD, Rainer Malik, PhD, Martin Dichgans, MD, Arne Lindgren, MD, PhD, Johan Wasselius, MD, PhD, Mattias Drake, student, Olle Melander, MD, PHD, Martin Stenman, MD, Andreea Ilinca, MD, Katherine Crawford, BS, Umme Lena, Bachelors of Arts, Farrah Mateen, MD, PhD, Hakan Ay, MD, Ona Wu, PhD, Markus Schirmer, PhD, Steve Cramer, MD, Polina Golland, PhD, Robert Brown, MD, MPH, James Meschia, MD, Owen A. Ross, PhD, Guillaume Pare, MD, MSc, FRCPC, Mike Chong, MSc, Tatjana Rundek, MD PhD, Katrina Gwinn, MD, Christopher Chen, BMBCh (Oxon), MRCP, FRCP, Jim Koenig, PhD, Eva Giralt, PhD, Danish Saleheen, MBBS, PhD, Frank-Erik de Leeuw, MD, PhD, Karin Klijn, MD, PhD, Yoichiro Kamatani, MD, PhD, Michiaki Kubo, MD, PhD, Yukinori Okada, MD, PhD, Annie Pedersen, MD, Maja Olsson, PhD, Juan José Martín, MD, Huichun Xu, MD, PhD, Eng King Tan, MD, Petrea Frid, MD, Chaeyoung Lee, PhD, David Tregouet, PhD, Thomas Leung, MB, ChB, MRCP, FHKCP, FHKAM, Richard Choy, BSc (Brad.), MSc(Med) (Birm.), PhD (CUHK), Christina Jern, MD, PhD, Keat Wei Loo, BSc, PhD, Gabriel Rinkel, MD, Paulo Franca, PhD, Iscia Cendes, MD, PhD, Caty Carrera, MD, Israel Fernandez-Cadenas, PhD, Joan Montaner, MD, PhD, Helen Kim, PhD, Mayowa Owolabi, MBBS, MSc, DrM, MWACP, FMCP, FAAN, FAS, Reecha Sofat, MD, Mark Bakker, PhD, Ynte Ruigrok, MD, PhD, Allard Hauer, PhD candidate, Sara L. Pulit, PhD, Sander W. van der Laan, PhD, Ryan Irvin, PhD, Murali Sargurupremraj, PhD, Alessandro Pezzini, MD, Foad Abd-Allah, MD, David Liebeskind, MD, Matthew Traylor, PhD, Rhea Tan, BSc (Hons), John Danesh, MD, DPhil, Loes Rutten-Jacobs, PhD, Amanda Donatti, PhD, student, Wagner Avelar, PhD, Joseph Broderick, MD, Daniel Woo, MD, MS, Cathie Sudlow, BMBCh, MSc, DPhil, FRCP, Kristiina Rannikmae, MD, Caitrin Wheeler McDonough, PhD, Tom van Agtmael, PhD, Matthew Walters, MD, MBChB, FRCP, Martin Söderholm, MD, PhD, Erik Lorentzen, Ph.Lic., Sandra Olsson, PhD, MSc, Tara Stanne, PhD, Martina Olsson, MSc, Rufus Akinyemi, PhD, MSc, MWACP, FMCP, Ioana Cotlatciuc, PhD, Patrick McArdle, PhD, Tushar Dave, MSc, Steven Kittner, MD, MPH, John Attia, MD, PhD, James E Faber, PhD, Iona Millwood, DPhil, Elsa Valdés Márquez, PhD, Michelangelo Mancuso, MD, PhD, Riina Vibo, MD, PhD, Janika Korv, MD, PhD, FESO, Jane Maguire, PhD, BN (Hons), BA, RN, Myriam Fornage, PhD, Jennifer Majersik, MD, Adam DeHavenon, MD, Matthew Alexander, MD, Michele Sale, PhD, Andrew Southerland, MD, MSc, Debra Owens, NNP, Bruce Psaty, MD, PhD, W. T. Longstreth, Jr, MD, MPH, Stacey Quintero Wolfe, MD, FAANS, Carl Langefeld, PhD, Carlos Cruchaga, PhD, Jan Konrad, administrative coordinator, Kevin Sheth, MD, Guido Falcone, MD, ScD, MPH, Kathleen Donahue, BS, Alexis N Simpkins, MD, PhD, Tan Wei Liang Byorn, MMBS, student, Bernard Chan, MD, Phil Clatworthy, MD, PhD, Jose Florez, MD, Eric Harshfield, PhD, Atsushi Hozawa, MD, Chung Hsu, MD, PhD, Chaur-Jong Hu, MD, PhD, Laure Ibanez, PhD, Masafumi Ihara, MD, PhD, FACP, Marcos Lange, PhD, Soo Ji Lee, PhD, MPH, I-Hui Lee, MD, PhD, Patricia Musolino, MD, PhD, Hirofumi Nakatomi, MD, PhD, Kwang-Yeol Park, MD, Stephen S Rich, PhD, Chris Riley, MBA, Joohon Sung, MD, PhD, Hideaki Suzuki, MD, PhD, Katie Vo, MD, Kazuo Washida, MD, PhD, Laura Garcia Ibenez, PhD, Agnieszka Slowik, MD, PhD, Albert Hofman, MD, PhD, Ale Algra, MD, MSc, Alex P Reiner, MD, MSc, Alexander S F Doney, PhD, Andreas Gschwendtner, MD, Andreea Ilinca, MD, Anne-Katrin Giese, MD, Arne Lindgren, MD, PhD, Astrid M Vicente, PhD, Bo Norrving, MD, PhD, Børge G Nordestgaard, MD, PhD, DMSc, Braxton D Mitchell, PhD, Bradford B Worrall, MD, MSc, Bruce M Psaty, MD, PhD, Cara L Carty, PhD, Cathie Sudlow, BMBCh, MSc, DPhil, FRCP, Christopher D Anderson, MD, Christopher Levi, MBBS B Med Sci FRACP, Claudia L Satizabal, PhD, Colin N A Palmer, PhD, Dale M Gamble, CCRP, Daniel Woo, MD, MS, Danish Saleheen, MBBS, PhD, E Bernd Ringelstein, MD, FAHA, Einar Valdimarsson, MD, Elizabeth Holliday, PhD, Gail Davies, PhD, Ganesh Chauhan, PhD, Gerard Pasterkamp, MD, PhD, Giorgio Boncoraglio, MD, Gregor Kuhlenbäumer, MD, PhD, Gudmar Thorleifsson, PhD, Guido J Falcone, MD, ScD, MPH, Guillame Pare, MD, MSc, FRCPC, Helena Schmidt, MD, PhD, Hossein Delavaran, MD, PhD, Hugh S Markus, MD, Hugo J Aparicio, MD, Ian Deary, PhD, Ioana Cotlarciuc, PhD, Israel Fernandez-Cadenas, PhD, James Meschia, MD, Jemma C Hopewell, PhD, FESC, Jingmin Liu, MSc, Joan Montaner, MD, PhD, Joanna Pera, MD, PhD, John Cole, MD, MS, John R Attia, MD, PhD, FRACP, FRCPC, Jonathan Rosand, MD, MSc, Jose M Ferro, MD, PhD, Joshua Bis, PhD, Karen Furie, MD, Kari Stefansson, MD, Klaus Berger, MD, PhD, Konstantinos Kostulas, MD, PhD, Kristina Rannikmae, MD, M Arfan Ikram, MD, PhD, Marianne Benn, MD, PhD, Martin Dichgans, MD, Martin Farrall, FRCPath, Massimo Pandolfo, MD, Matthew Traylor, PhD, Matthew Walters, MD, MBChB, FRCP, Michele Sale, PhD, Mike Nalls, PhD, Myriam Fornage, PhD, Natalie R van Zuydam, PhD, Pankaj Sharma, MD, PhD, Patricia Abrantes, PhD, Paul IW de Bakker, PhD, Peter Higgins, FRCP, Peter Lichtner, PhD, Peter M Rothwell, FMedSci, Philippe Amouyel, MD, PhD, Qiong Yang, PhD, Rainer Malik, PhD, Reinhold Schmidt, MD, Robert Clarke, MD, MRCP, FRCP, FFPH, Robin Lemmens, MD, PhD, Sander W van der Laan, PhD, Sara L Pulit, PhD, Sherine Abboud, MD, PhD, Sofia A Oliveira, PhD, Solveig Gretarsdottir, PhD, Stephanie Debette, MD, PhD, Stephen R Williams, PhD, Steve Bevan, BSc, PhD, Steven J Kittner, MD, Sudha Seshadri, MD, Thomas Mosley, PhD, Thomas WK Battey, BS, Turgut Tatlisumak, MD, PhD, Unnur Thorsteinsdottir, PhD, Vincent NS Thijs, MD, PhD, W T Longstreth, MD, Wei Zhao, MD, PhD, Wei-Min Chen, PhD, Yu-Ching Cheng, PhD, Marilyn S. Albert, PhD, Roger L. Albin, MD, Liana G. Apostolova, MD, Steven E. Arnold, MD, Sanjay Asthana, MD, Craig S. Atwood, PhD, Clinton T. Baldwin, PhD, M. Michael Barmada, PhD, Lisa L. Barnes, PhD, Sandra Barral, PhD, Thomas G. Beach, MD, PhD, James T. Becker, PhD, Gary W. Beecham, PhD, Duane Beekly, BS, David A. Bennett, MD, Eileen H. Bigio, MD, Thomas D. Bird, MD, Deborah Blacker, MD, ScD, Bradley F. Boeve, MD, Adam Boxer, MD, PhD, James R. Burke, MD, PhD, Jeffrey M. Burns, MD, MS, Joseph D. Buxbaum, PhD, Goldie S. Byrd, PhD, Guiqing Cai, MD, PhD, Nigel J. Cairns, PhD FRCPath, Laura B. Cantwell, MPH, Chuanhai Cao, PhD, Cynthia M. Carlsson, MD, MS, Regina M. Carney, MD, Minerva M. Carrasquillo, PhD, Steven L. Carroll, MD, PhD, Helena C. Chui, PhD, David G. Clark, MD, David H. Cribbs, PhD, Elizabeth A. Crocco, MD, Carlos Cruchaga, PhD, Philip L. De Jager, MD, PhD, Charles DeCarli, MD, F. Yesim Demirci, MD, Malcolm Dick, Dennis W. Dickson, MD, Ranjan Duara, Md, Nilufer Ertekin-Taner, MD, PhD, Denis A. Evans, MD, Kelley M. Faber, MS, M. Daniele Fallin, PhD, Kenneth B. Fallon, MD, David W. Fardo, PhD, Martin R. Farlow, MD, Lindsay A. Farrer, PhD, Steven Ferris, PhD, Tatiana M. Foroud, PhD, Matthew P. Frosch, MD, PhD, Douglas R. Galasko, MD, Marla Gearing, PhD, Daniel H. Geschwind, MD, PhD, Bernardino Ghetti, MD, John R. Gilbert, PhD, Rodney C.P. Go, PhD, Alison M. Goate, DPhil, Neill R. Graff-Radford, MD, Robert C. Green, MD, MPH, Patrick Griffith, MD, John H. Growdon, MD, Jonathan L. Haines, PhD, Hakon Hakonarson, MD, PhD, Ronald L. Hamilton, MD, Kara L. Hamilton-Nelson, MPH, Vahram Haroutunian, PhD, Lindy E. Harrell, MD, PhD, Lawrence S. Honig, MD, PhD, Ryan M. Huebinger, PhD, Christine M. Hulette, MD, Bradley T. Hyman, MD, PhD, Gregory A. Jicha, MD, PhD, Lee-Way Jin, MD, PhD, Gyungah Jun, PhD, M. Ilyas Kamboh, PhD, Anna Karydas, BA, John S.K. Kauwe, PhD, Jeffrey A. Kaye, MD, Ronald Kim, MD, Neil W. Kowall, MD, Joel H. Kramer, PsyD, Walter A. Kukull, PhD, Brian W. Kunkle, PhD, Frank M. LaFerla, PhD, James J. Lah, MD, PhD, Rosalyn Lang-Walker, PhD, Eric B. Larson, MD, MPH, James B. Leverenz, MD, Allan I. Levey, MD, PhD, Ge Li, MD, PhD, Andrew P. Lieberman, MD, PhD, Mark W. Logue, PhD, Oscar L. Lopez, MD, Kathryn L. Lunetta, PhD, Constantine G. Lyketsos, MD, Wendy J. Mack, PhD, Jennifer J. Manly, PhD, Daniel C. Marson, JD, PhD, Eden R. Martin, PhD, Frank Martiniuk, PhD, Deborah C. Mash, PhD, Eliezer Masliah, MD, Richard Mayeux, MD, Ann C. McKee, MD, Marsel Mesulam, MD, Bruce L. Miller, MD, Carol A. Miller, MD, Joshua W. Miller, PhD, Thomas J. Montine, MD, PhD, John C. Morris, MD, Jill R. Murrell, PhD, Adam C. Naj, PhD, Thomas O. Obisesan, MD, John M. Olichney, MD, Vernon S. Pankratz, PhD, Joseph E. Parisi, MD, Amanda Partch, MS, Henry L. Paulson, MD, PhD, Margaret A. Pericak-Vance, PhD, William Perry, BS, Elaine Peskind, MD, Ronald C. Petersen, MD, PhD, Aimee Pierce, MD, Wayne W. Poon, PhD, Huntington Potter, PhD, Joseph F. Quinn, MD, Ashok Raj, MD, Towfique Raj, PhD, Murray Raskind, MD, Eric M. Reiman, MD, Barry Reisberg, MD, Christiane Reitz, MD, PhD, John M. Ringman, MD, MS, Erik D. Roberson, MD, PhD, Howard J. Rosen, MD, Roger N. Rosenberg, MD, Mark A. Sager, MD, Mary Sano, PhD, Andrew J. Saykin, PsyD, Gerard D. Schellenberg, PhD, Julie A. Schneider, MD, MS, Lon S. Schneider, MD, MS, William W. Seeley, MD, Amanda G. Smith, MD, Joshua A. Sonnen, MD, Salvatore Spina, MD, Robert A. Stern, PhD, Russell H. Swerdlow, MD, Rudolph E. Tanzi, PhD, Tricia A. Thornton-Wells, PhD, John Q. Trojanowski, MD, PhD, Juan C. Troncoso, MD, Debby W. Tsuang, MD, Otto Valladares, MS, Vivianna M. Van Deerlin, MD, PhD, Linda J. Van Eldik, PhD, Badri N. Vardarajan, PhD, MS, Harry V. Vinters, MD, Jean Paul Vonsattel, MD, Li-San Wang, PhD, Sandra Weintraub, PhD, Kathleen A. Welsh-Bohmer, PhD, Jennifer Williamson, MS, MPH, Thomas S. Wingo, MD, Sarah Wishnek, MPH, Randall L. Woltjer, MD, PhD, Clinton B. Wright, MD, MS, Steven G. Younkin, MD, PhD, Chang-En Yu, PhD, Lei Yu, PhD, Ganesh Chauhan, PhD, Audrey Y. Chu, PhD, Myriam Fornage, PhD, Joshua C. Bis, PhD, Aki S. Havulinna, DSc, Muralidharan Sargurupremraj, PhD, Albert Vernon Smith, PhD, Hieab H.H. Adams, MSc, Seung Hoan Choi, MA, Stella Trompet, PhD, Melissa E. Garcia, MPH, Ani Manichaikul, PhD, Alexander Teumer, PhD, Stefan Gustafsson, PhD, Traci M. Bartz, MS, Céline Bellenguez, PhD, Jean Sebastien Vidal, MD, Xueqiu Jian, PhD, Olafur Kjartansson, MD, Kerri L. Wiggins, MS, Claudia L. Satizabal, PhD, Flora Xue, MS, Samuli Ripatti, PhD, Yongmei Liu, PhD, Joris Deelen, PhD, Marcel den Hoed, PhD, Susan R. Heckbert, MD, Kenneth Rice, PhD, Nicholas L. Smith, PhD, Quenna Wong, MS, Hugo J. Aparicio, MD, Julie E. Buring, ScD, Paul M Ridker, MD, Claudine Berr, MD, Jean-François Dartigues, MD, Anders Hamsten, MD, Patrik K. Magnusson, PhD, Nancy L. Pedersen, PhD, Lars Lannfelt, MD, Lars Lind, MD, Cecilia M. Lindgren, PhD, Andrew P. Morris, PhD, Albert Hofman, MD, Peter J. Koudstaal, MD, Marileen LP. Portegies, MD, André G. Uitterlinden, PhD, Anton JM de Craen, PhD, Ian Ford, MD, J. Wouter Jukema, MD, David J Stott, MD, Norrina B. Allen, PhD, Michele M. Sale, PhD, Andrew D Johnson, PhD, David A. Bennett, MD, Philip L. De Jager, MD, PhD, Charles C. White, PhD, Hans Jörgen Grabe, MD, Marcello Ricardo Paulista Markus, MD, Oscar L Lopez, MD, Jerome I. Rotter, MD, Michael A. Nalls, PhD, Rebecca F. Gottesman, MD, Michael E. Griswold, PhD, David S. Knopman, MD, B. Gwen Windham, MD, Alexa Beiser, PhD, Erkki Vartiainen, MD, Curtis R. French, PhD, Tobias Kurth, MD, Bruce M. Psaty, MD, Tamara B. Harris, MD, Stephen S Rich, PhD, Anita L. deStefano, PhD, Carsten Oliver Schmidt, PhD, Veikko Salomaa, MD, Thomas H. Mosley, PhD, Erik Ingelsson, MD, PhD, Cornelia M. van Duijn, PhD, Christophe Tzourio, MD, Lenore J Launer, PhD, M. Arfan Ikram, MD, Daniel I. Chasman, PhD, W. T. Longstreth, Jr, MD, MPH, Sudha Seshadri, MD, Stéphanie Debette, MD, Benjamin F.J. Verhaaren, MD, PhD, Stéphanie Debette, MD, PhD, Joshua C. Bis, PhD, Jennifer A. Smith, PhD, MPH, MA, M. Kamran Ikram, MD, PhD, Hieab H. Adams, MSc, Ashley H. Beecham, MSc, Kumar B. Rajan, PhD, Lorna M. Lopez, PhD, Sandra Barral, PhD, Mark A. van Buchem, MD, PhD, Jeroen van der Grond, PhD, Albert V. Smith, PhD, Katrin Hegenscheid, MD, Neelum T. Aggarwal, MD, Mariza de Andrade, PhD, Elizabeth J. Atkinson, PhD, Marian Beekman, PhD, Alexa S. Beiser, PhD, Susan H. Blanton, PhD, Eric Boerwinkle, PhD, Adam M. Brickman, PhD, R. Nick Bryan, MD, PhD, Ganesh Chauhan, PhD, Christopher P.L.H. Chen, FRCP, Vincent Chouraki, MD, PhD, Anton J.M. de Craen, PhD, Fabrice Crivello, PhD, Ian J. Deary, PhD, Joris Deelen, MSc, Philip L. De Jager, MD, PhD, Carole Dufouil, PhD, Mitchell S.V. Elkind, MD, MSc, Denis A. Evans, MD, Paul Freudenberger, MSc, Rebecca F. Gottesman, MD, PhD, Vilmundur Guðnason, MD, PhD, Mohamad Habes, PhD, Susan R. Heckbert, MD, PhD, Gerardo Heiss, MD, Saima Hilal, MBBS, Edith Hofer, PhD, Albert Hofman, MD, PhD, Carla A. Ibrahim-Verbaas, MD, David S. Knopman, MD, Cora E. Lewis, MD, MSPH, Jiemin Liao, MSc, David C.M. Liewald, BSc, Michelle Luciano, PhD, Aad van der Lugt, MD, PhD, Oliver O. Martinez, PhD, Richard Mayeux, MD, MSc, Bernard Mazoyer, MD, PhD, Mike Nalls, PhD, Matthias Nauck, MD, Wiro J. Niessen, PhD, Ben A. Oostra, PhD, Bruce M. Psaty, MD, PhD, Kenneth M. Rice, PhD, Jerome I. Rotter, MD, Bettina von Sarnowski, MD, Helena Schmidt, MD, PhD, Pamela J. Schreiner, PhD, Maaike Schuur, MD, PhD, Stephen S. Sidney, MD, MPH, Sigurdur Sigurdsson, MSc, P. Eline Slagboom, PhD, David J.M. Stott, MD, John C. van Swieten, MD, PhD, Alexander Teumer, PhD, Anna Maria Töglhofer, MSc, Matthew Traylor, PhD, Stella Trompet, PhD, Stephen T. Turner, MD, Christophe Tzourio, MD, PhD, Hae-Won Uh, PhD, André G. Uitterlinden, PhD, Meike W. Vernooij, MD, PhD, Jing J. Wang, PhD, Tien Y. Wong, MD, PhD, Joanna M. Wardlaw, MD, B. Gwen Windham, MD, Katharina Wittfeld, MS, Christiane Wolf, PhD, Clinton B. Wright, MD, Qiong Yang, PhD, Wei Zhao, MD, PhD, Alex Zijdenbos, PhD, J. Wouter Jukema, MD, PhD, Ralph L. Sacco, MD, Sharon L.R. Kardia, PhD, Philippe Amouyel, MD, PhD, Thomas H. Mosley, PhD, W. T. Longstreth, Jr, MD, MPH, Charles C. DeCarli, MD, Cornelia M. van Duijn, PhD, Reinhold Schmidt, MD, Lenore J. Launer, PhD, Hans J. Grabe, MD, Sudha S. Seshadri, MD, M. Arfan Ikram, MD, PhD, Myriam Fornage, PhD, Joshua C. Bis, PhD, Maryam Kavousi, MD, MSc, Nora Franceschini, MD, MPH, Aaron Isaacs, PhD, Gonçalo R Abecasis, PhD, Ulf Schminke, MD, Wendy Post, MD, Albert V. Smith, PhD, L. Adrienne Cupples, PhD, Hugh S Markus, MD, Reinhold Schmidt, MD, Jennifer E. Huffman, MSc, Terho Lehtimäki, MD, PhD, Jens Baumert, PhD, Thomas Münzel, MD, Susan R. Heckbert, MD, PhD, Abbas Dehghan, MD, PhD, Kari North, PhD, Ben Oostra, PhD, Steve Bevan, PhD, Eva-Maria Stoegerer, MD, Caroline Hayward, PhD, Olli Raitakari, MD, PhD, Christa Meisinger, MD, MPH, Arne Schillert, PhD, Serena Sanna, PhD, Henry Völzke, MD, Yu-Ching Cheng, PhD, Bolli Thorsson, MD, Caroline S. Fox, MD, MS, Kenneth Rice, PhD, Fernando Rivadeneira, MD, PhD, Vijay Nambi, MD, Eran Halperin, PhD, Katja E. Petrovic, MSc, Leena Peltonen, MD, PhD, H. Erich Wichmann, MD, PhD, Renate B. Schnabel, MD, MSc, Marcus Dörr, MD, Afshin Parsa, MD, MPH, Thor Aspelund, PhD, Serkalem Demissie, PhD, Sekar Kathiresan, MD, Muredach P. Reilly, MBBCH, MSCE, Kent Taylor, PhD, Andre Uitterlinden, PhD, David J. Couper, PhD, Matthias Sitzer, MD, Mika Kähönen, MD, PhD, Thomas Illig, PhD, Philipp S. Wild, MD, Marco Orru, MD, Jan Lüdemann, PhD, Alan R. Shuldiner, MD, Gudny Eiriksdottir, MSc, Charles C. White, MPH, Jerome I. Rotter, MD, Albert Hofman, MD, PhD, Jochen Seissler, MD, Tanja Zeller, PhD, Gianluca Usala, PhD, Florian Ernst, PhD, Lenore J. Launer, PhD, Ralph B. D'Agostino, Sr, PhD, Daniel H. O'Leary, MD, Christie Ballantyne, MD, Joachim Thiery, MD, MBA, Andreas Ziegler, Dr. rer. nat. habil., Edward G. Lakatta, MD, Ravi Kumar Chilukoti, MSc, Tamara B. Harris, MD, PhD, Philip A. Wolf, MD, Bruce M. Psaty, MD, PhD, Joseph F Polak, MD, MPH, Xia Li, MD, MPH, Wolfgang Rathmann, MD, MSPH, Manuela Uda, PhD, Eric Boerwinkle, PhD, Norman Klopp, PhD, Helena Schmidt, MD PhD, James F Wilson, DPhil, Jorma Viikari, MD, PhD, Wolfgang Koenig, MD, Stefan Blankenberg, Prof Dr med, Anne B. Newman, MD, MPH, Jacqueline Witteman, PhD, Gerardo Heiss, MD, PhD, Cornelia van Duijn, PhD, Angelo Scuteri, MD, PhD, Georg Homuth, PhD, Braxton D. Mitchell, PhD, Vilmundur Gudnason, MD, PhD, and Christopher J. O’Donnell, MD, MPH, Læknadeild (HÍ), Faculty of Medicine (UI), Heilbrigðisvísindasvið (HÍ), School of Health Sciences (UI), Háskóli Íslands, University of Iceland, and Berr, Claudine
Subjects: Neurology & Neurosurgery, [SDV]Life Sciences [q-bio], Heilaskaði, Clinical Neurology, Stroke Genetics Network (SiGN), the International Stroke Genetics Consortium (ISGC), METASTROKE, Alzheimer's Disease Genetics Consortium (ADGC), and the Neurology Working Group of the Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) Consortium, R1, Article, [SDV] Life Sciences [q-bio], Taugasjúkdómar, [SDV.SPEE] Life Sciences [q-bio]/Santé publique et épidémiologie, Meta-analyses, Brain infarcts, GWAS, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, ddc:610, Erfðarannsóknir, MRI
Abstract: Publisher's version (útgefin grein), Objective: To explore genetic and lifestyle risk factors of MRI-defined brain infarcts (BI) in large population-based cohorts. Methods We performed meta-analyses of genome-wide association studies (GWAS) and examined associations of vascular risk factors and their genetic risk scores (GRS) with MRI-defined BI and a subset of BI, namely, small subcortical BI (SSBI), in 18 population-based cohorts (n=20,949) from 5 ethnicities (3,726 with BI, 2,021 with SSBI). Top loci were followed up in 7 population-based cohorts (n = 6,862; 1,483 with BI, 630 with SBBI), and we tested associations with related phenotypes including ischemic stroke and pathologically defined BI. Results: The mean prevalence was 17.7% for BI and 10.5% for SSBI, steeply rising after age 65. Two loci showed genome-wide significant association with BI: FBN2, p = 1.77 × 10-8; and LINC00539/ZDHHC20, p = 5.82 × 10-9. Both have been associated with blood pressure (BP)-related phenotypes, but did not replicate in the smaller follow-up sample or show associations with related phenotypes. Age- and sex-adjusted associations with BI and SSBI were observed for BP traits (p value for BI, p[BI] = 9.38 × 10-25; p [SSBI] = 5.23 × 10-14 for hypertension), smoking (p[BI]= 4.4 × 10-10; p [SSBI] = 1.2 × 10 -4), diabetes (p[BI] = 1.7 × 10 -8; p [SSBI] = 2.8 × 10 -3), previous cardiovascular disease (p [BI] = 1.0 × 10-18; p [SSBI] = 2.3 × 10-7), stroke (p [BI] = 3.9 × 10-69; p [SSBI] = 3.2 × 10 -24), and MRI-defined white matter hyperintensity burden (p [BI]=1.43 × 10-157; p [SSBI] = 3.16 × 10-106), but not with body mass index or cholesterol. GRS of BP traits were associated with BI and SSBI (p ≤ 0.0022), without indication of directional pleiotropy. Conclusion: In this multiethnic GWAS meta-analysis, including over 20,000 population-based participants, we identified genetic risk loci for BI requiring validation once additional large datasets become available. High BP, including genetically determined, was the most significant modifiable, causal risk factor for BI., CHAP: R01-AG-11101, R01-AG-030146, NIRP-14-302587. SMART: This study was supported by a grant from the Netherlands Organization for Scientific Research–Medical Sciences (project no. 904-65–095). LBC: The authors thank the LBC1936 participants and the members of the LBC1936 research team who collected and collated the phenotypic and genotypic data. The LBC1936 is supported by Age UK (Disconnected Mind Programme grant). The work was undertaken by The University of Edinburgh Centre for Cognitive Ageing and Cognitive Epidemiology, part of the cross-council Lifelong Health and Wellbeing Initiative (MR/K026992/1). The brain imaging was performed in the Brain Research Imaging Centre (https://www.ed.ac.uk/clinical-sciences/edinburgh-imaging), a center in the SINAPSE Collaboration (sinapse.ac.uk) supported by the Scottish Funding Council and Chief Scientist Office. Funding from the UK Biotechnology and Biological Sciences Research Council (BBSRC) and the UK Medical Research Council is acknowledged. Genotyping was supported by a grant from the BBSRC (ref. BB/F019394/1). PROSPER: The PROSPER study was supported by an investigator-initiated grant obtained from Bristol-Myers Squibb. Prof. Dr. J.W. Jukema is an Established Clinical Investigator of the Netherlands Heart Foundation (grant 2001 D 032). Support for genotyping was provided by the seventh framework program of the European commission (grant 223004) and by the Netherlands Genomics Initiative (Netherlands Consortium for Healthy Aging grant 050-060-810). SCES and SiMES: National Medical Research Council Singapore Centre Grant NMRC/CG/013/2013. C.-Y.C. is supported by the National Medical Research Council, Singapore (CSA/033/2012), Singapore Translational Research Award (STaR) 2013. Dr. Kamran Ikram received additional funding from the Singapore Ministry of Health's National Medical Research Council (NMRC/CSA/038/2013). SHIP: SHIP is part of the Community Medicine Research net of the University of Greifswald, Germany, which is funded by the Federal Ministry of Education and Research (grants no. 01ZZ9603, 01ZZ0103, and 01ZZ0403), the Ministry of Cultural Affairs, as well as the Social Ministry of the Federal State of Mecklenburg–West Pomerania, and the network “Greifswald Approach to Individualized Medicine (GANI_MED)” funded by the Federal Ministry of Education and Research (grant 03IS2061A). Genome-wide data have been supported by the Federal Ministry of Education and Research (grant no. 03ZIK012) and a joint grant from Siemens Healthineers, Erlangen, Germany, and the Federal State of Mecklenburg–West Pomerania. Whole-body MRI was supported by a joint grant from Siemens Healthineers, Erlangen, Germany, and the Federal State of Mecklenburg–West Pomerania. The University of Greifswald is a member of the Caché Campus program of the InterSystems GmbH. OATS (Older Australian Twins Study): OATS was supported by an Australian National Health and Medical Research Council (NHRMC)/Australian Research Council (ARC) Strategic Award (ID401162) and by a NHMRC grant (ID1045325). OATS was facilitated via access to the Australian Twin Registry, which is supported by the NHMRC Enabling Grant 310667. The OATS genotyping was partly supported by a Commonwealth Scientific and Industrial Research Organisation Flagship Collaboration Fund Grant. NOMAS: The Northern Manhattan Study is funded by the NIH grant “Stroke Incidence and Risk Factors in a Tri-Ethnic Region” (NINDS R01NS 29993). TASCOG: NHMRC and Heart Foundation. AGES: The study was funded by the National Institute on Aging (NIA) (N01-AG-12100), Hjartavernd (the Icelandic Heart Association), and the Althingi (the Icelandic Parliament), with contributions from the Intramural Research Programs at the NIA, the National Heart, Lung, and Blood Institute (NHLBI), and the National Institute of Neurological Disorders and Stroke (NINDS) (Z01 HL004607-08 CE). ERF: The ERF study as a part of European Special Populations Research Network (EUROSPAN) was supported by European Commission FP6 STRP grant no. 018947 (LSHG-CT-2006-01947) and also received funding from the European Community's Seventh Framework Programme (FP7/2007–2013)/grant agreement HEALTH-F4-2007-201413 by the European Commission under the programme “Quality of Life and Management of the Living Resources” of 5th Framework Programme (no. QLG2-CT-2002-01254). High-throughput analysis of the ERF data was supported by a joint grant from Netherlands Organization for Scientific Research and the Russian Foundation for Basic Research (NWO-RFBR 047.017.043). Exome sequencing analysis in ERF was supported by the ZonMw grant (project 91111025). Najaf Amin is supported by the Netherlands Brain Foundation (project no. F2013[1]-28). ARIC: The Atherosclerosis Risk in Communities study was performed as a collaborative study supported by NHLBI contracts (HHSN268201100005C, HSN268201100006C, HSN268201100007C, HHSN268201100008C, HHSN268201100009C, HHSN268201100010C, HHSN268201100011C, and HHSN268201100012C), R01HL70825, R01HL087641, R01HL59367, and R01HL086694; National Human Genome Research Institute contract U01HG004402; and NIH contract HHSN268200625226C. Infrastructure was partly supported by grant no. UL1RR025005, a component of the NIH and NIH Roadmap for Medical Research. This project was also supported by NIH R01 grant NS087541 to M.F. FHS: This work was supported by the National Heart, Lung and Blood Institute's Framingham Heart Study (contracts no. N01-HC-25195 and no. HHSN268201500001I), and its contract with Affymetrix, Inc. for genotyping services (contract no. N02-HL-6-4278). A portion of this research utilized the Linux Cluster for Genetic Analysis (LinGA-II) funded by the Robert Dawson Evans Endowment of the Department of Medicine at Boston University School of Medicine and Boston Medical Center. This study was also supported by grants from the NIA (R01s AG033040, AG033193, AG054076, AG049607, AG008122, and U01-AG049505) and the NINDS (R01-NS017950, UH2 NS100605). Dr. DeCarli is supported by the Alzheimer's Disease Center (P30 AG 010129). ASPS: The research reported in this article was funded by the Austrian Science Fund (FWF) grant nos. P20545-P05, P13180, and P20545-B05, by the Austrian National Bank Anniversary Fund, P15435, and the Austrian Ministry of Science under the aegis of the EU Joint Programme–Neurodegenerative Disease Research (JPND) (jpnd.eu). LLS: The Leiden Longevity Study has received funding from the European Union's Seventh Framework Programme (FP7/2007–2011) under grant agreement no. 259679. This study was supported by a grant from the Innovation-Oriented Research Program on Genomics (SenterNovem IGE05007), the Centre for Medical Systems Biology, and the Netherlands Consortium for Healthy Ageing (grant 050-060-810), all in the framework of the Netherlands Genomics Initiative, Netherlands Organization for Scientific Research (NWO), UnileverColworth, and by BBMRI-NL, a Research Infrastructure financed by the Dutch government (NWO 184.021.007). CHS: This CHS research was supported by contracts HHSN268201200036C, HHSN268200800007C, N01HC55222, N01HC85079, N01HC85080, N01HC85081, N01HC85082, N01HC85083, N01HC85086, N01HC15103, and HHSN268200960009C and grants U01HL080295, R01HL087652, R01HL105756, R01HL103612, R01HL120393, R01HL085251, and R01HL130114 from the NHLBI with additional contribution from NINDS. Additional support was provided through R01AG023629 from the NIA. A full list of principal CHS investigators and institutions can be found at CHS-NHLBI.org. The provision of genotyping data was supported in part by the National Center for Advancing Translational Sciences, CTSI grant UL1TR001881, and the National Institute of Diabetes and Digestive and Kidney Disease Diabetes Research Center grant DK063491 to the Southern California Diabetes Endocrinology Research Center. The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH. Rotterdam Study: The generation and management of GWAS genotype data for the Rotterdam Study is supported by the Netherlands Organisation of Scientific Research (NWO) Investments (no. 175.010.2005.011, 911-03-012). This study is funded by the Research Institute for Diseases in the Elderly (014-93-015; RIDE2), the Netherlands Genomics Initiative (NGI)/NWO project no. 050-060-810. The Rotterdam Study is funded by Erasmus MC Medical Center and Erasmus MC University, Rotterdam, Netherlands Organization for Health Research and Development (ZonMw), the Research Institute for Diseases in the Elderly (RIDE), the Ministry of Education, Culture and Science, the Ministry for Health, Welfare and Sports, the European Commission (DG XII), and the Municipality of Rotterdam. M.A.I. is supported by an NWO Veni grant (916.13.054). The 3-City Study: The 3-City Study is conducted under a partnership agreement among the Institut National de la Santé et de la Recherche Médicale (INSERM), the University of Bordeaux, and Sanofi-Aventis. The Fondation pour la Recherche Médicale funded the preparation and initiation of the study. The 3C Study is also supported by the Caisse Nationale Maladie des Travailleurs Salariés, Direction Générale de la Santé, Mutuelle Générale de l’Education Nationale (MGEN), Institut de la Longévité, Conseils Régionaux of Aquitaine and Bourgogne, Fondation de France, and Ministry of Research–INSERM Programme “Cohortes et collections de données biologiques.” C.T. and S.D. have received investigator-initiated research funding from the French National Research Agency (ANR) and from the Fondation Leducq. S.D. is supported by a starting grant from the European Research Council (SEGWAY), a grant from the Joint Programme of Neurodegenerative Disease research (BRIDGET), from the European Union's Horizon 2020 research and innovation programme under grant agreements No 643417 & No 640643, and by the Initiative of Excellence of Bordeaux University. Part of the computations were performed at the Bordeaux Bioinformatics Center (CBiB), University of Bordeaux. This work was supported by the National Foundation for Alzheimer's Disease and Related Disorders, the Institut Pasteur de Lille, the Labex DISTALZ, and the Centre National de Génotypage. ADGC: The Alzheimer Disease Genetics Consortium is supported by NIH. NIH-NIA supported this work through the following grants: ADGC, U01 AG032984, RC2 AG036528; NACC, U01 AG016976; NCRAD, U24 AG021886; NIA LOAD, U24 AG026395, U24 AG026390; Banner Sun Health Research Institute, P30 AG019610; Boston University, P30 AG013846, U01 AG10483, R01 CA129769, R01 MH080295, R01 AG017173, R01 AG025259, R01AG33193; Columbia University, P50 AG008702, R37 AG015473; Duke University, P30 AG028377, AG05128; Emory University, AG025688; Group Health Research Institute, UO1 AG06781, UO1 HG004610; Indiana University, P30 AG10133; Johns Hopkins University, P50 AG005146, R01 AG020688; Massachusetts General Hospital, P50 AG005134; Mayo Clinic, P50 AG016574; Mount Sinai School of Medicine, P50 AG005138, P01 AG002219; New York University, P30 AG08051, MO1RR00096, UL1 RR029893, 5R01AG012101, 5R01AG022374, 5R01AG013616, 1RC2AG036502, 1R01AG035137; Northwestern University, P30 AG013854; Oregon Health & Science University, P30 AG008017, R01 AG026916; Rush University, P30 AG010161, R01 AG019085, R01 AG15819, R01 AG17917, R01 AG30146; TGen, R01 NS059873; University of Alabama at Birmingham, P50 AG016582, UL1RR02777; University of Arizona, R01 AG031581; University of California, Davis, P30 AG010129; University of California, Irvine, P50 AG016573, P50, P50 AG016575, P50 AG016576, P50 AG016577; University of California, Los Angeles, P50 AG016570; University of California, San Diego, P50 AG005131; University of California, San Francisco, P50 AG023501, P01 AG019724; University of Kentucky, P30 AG028383, AG05144; University of Michigan, P50 AG008671; University of Pennsylvania, P30 AG010124; University of Pittsburgh, P50 AG005133, AG030653; University of Southern California, P50 AG005142; University of Texas Southwestern, P30 AG012300; University of Miami, R01 AG027944, AG010491, AG027944, AG021547, AG019757; University of Washington, P50 AG005136; Vanderbilt University, R01 AG019085; and Washington University, P50 AG005681, P01 AG03991. The Kathleen Price Bryan Brain Bank at Duke University Medical Center is funded by NINDS grant NS39764, NIMH MH60451, and by GlaxoSmithKline. Genotyping of the TGEN2 cohort was supported by Kronos Science. The TGen series was also funded by NIA grant AG041232, the Banner Alzheimer's Foundation, The Johnnie B. Byrd Sr. Alzheimer's Institute, the Medical Research Council, and the state of Arizona and also includes samples from the following sites: Newcastle Brain Tissue Resource (funding via the Medical Research Council [MRC], local NHS trusts, and Newcastle University), MRC London Brain Bank for Neurodegenerative Diseases (funding via the Medical Research Council), South West Dementia Brain Bank (funding via numerous sources including the Higher Education Funding Council for England [HEFCE], Alzheimer's Research Trust [ART], BRACE, as well as North Bristol NHS Trust Research and Innovation Department and DeNDRoN), The Netherlands Brain Bank (funding via numerous sources including Stichting MS Research, Brain Net Europe, Hersenstichting Nederland Breinbrekend Werk, International Parkinson Fonds, Internationale Stiching Alzheimer Onderzoek), Institut de Neuropatologia, Servei Anatomia Patologica, and Universitat de Barcelona). ADNI: Funding for ADNI is through the Northern California Institute for Research and Education by grants from Abbott, AstraZeneca AB, Bayer Schering Pharma AG, Bristol-Myers Squibb, Eisai Global Clinical Development, Elan Corporation, Genentech, GE Healthcare, GlaxoSmithKline, Innogenetics, Johnson & Johnson, Eli Lilly and Co., Medpace, Inc., Merck and Co., Inc., Novartis AG, Pfizer Inc, F. Hoffman-La Roche, Schering-Plough, Synarc, Inc., Alzheimer's Association, Alzheimer's Drug Discovery Foundation, the Dana Foundation, and the National Institute of Biomedical Imaging and Bioengineering and NIA grants U01 AG024904, RC2 AG036535, and K01 AG030514. Support was also provided by the Alzheimer's Association (LAF, IIRG-08-89720; MAP-V, IIRG-05-14147) and the US Department of Veterans Affairs Administration, Office of Research and Development, Biomedical Laboratory Research Program. SiGN: Stroke Genetic Network (SiGN) was supported in part by award nos. U01NS069208 and R01NS100178 from NINDS. Genetics of Early-Onset Stroke (GEOS) Study was supported by the NIH Genes, Environment and Health Initiative (GEI) grant U01 HG004436, as part of the GENEVA consortium under GEI, with additional support provided by the Mid-Atlantic Nutrition and Obesity Research Center (P30 DK072488); and the Office of Research and Development, Medical Research Service, and the Baltimore Geriatrics Research, Education, and Clinical Center of the Department of Veterans Affairs. Genotyping services were provided by the Johns Hopkins University Center for Inherited Disease Research (CIDR), which is fully funded through a federal contract from the NIH to Johns Hopkins University (contract no. HHSN268200782096C). Assistance with data cleaning was provided by the GENEVA Coordinating Center (U01 HG 004446; PI Bruce S. Weir). Study recruitment and assembly of datasets were supported by a Cooperative Agreement with the Division of Adult and Community Health, Centers for Disease Control and Prevention, and by grants from NINDS and the NIH Office of Research on Women's Health (R01 NS45012, U01 NS069208-01). METASTROKE: ASGC: Australian population control data were derived from the Hunter Community Study. This research was funded by grants from the Australian National and Medical Health Research Council (NHMRC Project Grant ID: 569257), the Australian National Heart Foundation (NHF Project Grant ID: G 04S 1623), the University of Newcastle, the Gladys M Brawn Fellowship scheme, and the Vincent Fairfax Family Foundation in Australia. E.G.H. was supported by a Fellowship from the NHF and National Stroke Foundation of Australia (ID: 100071). J.M. was supported by an Australian Postgraduate Award. BRAINS: Bio-Repository of DNA in Stroke (BRAINS) is partly funded by a Senior Fellowship from the Department of Health (UK) to P.S., the Henry Smith Charity, and the UK-India Education Research Institutive (UKIERI) from the British Council. GEOS: Genetics of Early Onset Stroke (GEOS) Study, Baltimore, was supported by GEI Grant U01 HG004436, as part of the GENEVA consortium under GEI, with additional support provided by the Mid-Atlantic Nutrition and Obesity Research Center (P30 DK072488), and the Office of Research and Development, Medical Research Service, and the Baltimore Geriatrics Research, Education, and Clinical Center of the Department of Veterans Affairs. Genotyping services were provided by the Johns Hopkins University Center for Inherited Disease Research (CIDR), which is fully funded through a federal contract from the NIH to the Johns Hopkins University (contract no. HHSN268200782096C). Assistance with data cleaning was provided by the GENEVA Coordinating Center (U01 HG 004446; PI Bruce S. Weir). Study recruitment and assembly of datasets were supported by a Cooperative Agreement with the Division of Adult and Community Health, Centers for Disease Control and Prevention, and by grants from NINDS and the NIH Office of Research on Women's Health (R01 NS45012, U01 NS069208-01). HPS: Heart Protection Study (HPS) (ISRCTN48489393) was supported by the UK MRC, British Heart Foundation, Merck and Co. (manufacturers of simvastatin), and Roche Vitamins Ltd. (manufacturers of vitamins). Genotyping was supported by a grant to Oxford University and CNG from Merck and Co. J.C.H. acknowledges support from the British Heart Foundation (FS/14/55/30806). ISGS: Ischemic Stroke Genetics Study (ISGS)/Siblings With Ischemic Stroke Study (SWISS) was supported in part by the Intramural Research Program of the NIA, NIH project Z01 AG-000954-06. ISGS/SWISS used samples and clinical data from the NIH-NINDS Human Genetics Resource Center DNA and Cell Line Repository (ccr.coriell.org/ninds), human subjects protocol nos. 2003-081 and 2004-147. ISGS/SWISS used stroke-free participants from the Baltimore Longitudinal Study of Aging (BLSA) as controls. The inclusion of BLSA samples was supported in part by the Intramural Research Program of the NIA, NIH project Z01 AG-000015-50, human subjects protocol no. 2003-078. The ISGS study was funded by NIH-NINDS Grant R01 NS-42733 (J.F.M.). The SWISS study was funded by NIH-NINDS Grant R01 NS-39987 (J.F.M.). This study used the high-performance computational capabilities of the Biowulf Linux cluster at the NIH (biowulf.nih.gov). MGH-GASROS: MGH Genes Affecting Stroke Risk and Outcome Study (MGH-GASROS) was supported by NINDS (U01 NS069208), the American Heart Association/Bugher Foundation Centers for Stroke Prevention Research 0775010N, the NIH and NHLBI's STAMPEED genomics research program (R01 HL087676), and a grant from the National Center for Research Resources. The Broad Institute Center for Genotyping and Analysis is supported by grant U54 RR020278 from the National Center for Research resources. Milan: Milano–Besta Stroke Register Collection and genotyping of the Milan cases within CEDIR were supported by the Italian Ministry of Health (grant nos.: RC 2007/LR6, RC 2008/LR6; RC 2009/LR8; RC 2010/LR8; GR-2011-02347041), FP6 LSHM-CT-2007-037273 for the PROCARDIS control samples. WTCCC2: Wellcome Trust Case-Control Consortium 2 (WTCCC2) was principally funded by the Wellcome Trust, as part of the Wellcome Trust Case Control Consortium 2 project (085475/B/08/Z and 085475/Z/08/Z and WT084724MA). The Stroke Association provided additional support for collection of some of the St George's, London cases. The Oxford cases were collected as part of the Oxford Vascular Study, which is funded by the MRC, Stroke Association, Dunhill Medical Trust, National Institute of Health Research (NIHR), and the NIHR Biomedical Research Centre, Oxford. The Edinburgh Stroke Study was supported by the Wellcome Trust (clinician scientist award to C.L.M.S.) and the Binks Trust. Sample processing occurred in the Genetics Core Laboratory of the Wellcome Trust Clinical Research Facility, Western General Hospital, Edinburgh. Much of the neuroimaging occurred in the Scottish Funding Council Brain Imaging Research Centre (https://www.ed.ac.uk/clinical-sciences/edinburgh-imaging), Division of Clinical Neurosciences, University of Edinburgh, a core area of the Wellcome Trust Clinical Research Facility, and part of the SINAPSE (Scottish Imaging Network: A Platform for Scientific Excellence) collaboration (sinapse.ac.uk), funded by the Scottish Funding Council and the Chief Scientist Office. Collection of the Munich cases and data analysis was supported by the Vascular Dementia Research Foundation. This project has received funding from the European Union's Horizon 2020 research and innovation programme under grant agreements no. 666881, SVDs@target (to M.D.) and no. 667375, CoSTREAM (to M.D.); the DFG as part of the Munich Cluster for Systems Neurology (EXC 1010 SyNergy) and the CRC 1123 (B3) (to M.D.); the Corona Foundation (to M.D.); the Fondation Leducq (Transatlantic Network of Excellence on the Pathogenesis of Small Vessel Disease of the Brain) (to M.D.); the e:Med program (e:AtheroSysMed) (to M.D.) and the FP7/2007-2103 European Union project CVgenes@target (grant agreement no. Health-F2-2013-601456) (to M.D.). M.F. and A.H. acknowledge support from the BHF Centre of Research Excellence in Oxford and the Wellcome Trust core award (090532/Z/09/Z). VISP: The GWAS component of the Vitamin Intervention for Stroke Prevention (VISP) study was supported by the US National Human Genome Research Institute (NHGRI), grant U01 HG005160 (PI Michèle Sale and Bradford Worrall), as part of the Genomics and Randomized Trials Network (GARNET). Genotyping services were provided by the Johns Hopkins University Center for Inherited Disease Research (CIDR), which is fully funded through a federal contract from the NIH to Johns Hopkins University. Assistance with data cleaning was provided by the GARNET Coordinating Center (U01 HG005157; PI Bruce S. Weir). Study recruitment and collection of datasets for the VISP clinical trial were supported by an investigator-initiated research grant (R01 NS34447; PI James Toole) from the US Public Health Service, NINDS, Bethesda, MD. Control data obtained through the database of genotypes and phenotypes (dbGAP) maintained and supported by the United States National Center for Biotechnology Information, US National Library of Medicine. WHI: Funding support for WHI-GARNET was provided through the NHGRI GARNET (grant no. U01 HG005152). Assistance with phenotype harmonization and genotype cleaning, as well as with general study coordination, was provided by the GARNET Coordinating Center (U01 HG005157). Funding support for genotyping, which was performed at the Broad Institute of MIT and Harvard, was provided by the GEI (U01 HG004424). R.L. is a senior clinical investigator of FWO Flanders. F.W.A. is supported by a Dekker scholarship-Junior Staff Member 2014T001–Netherlands Heart Foundation and UCL Hospitals NIHR Biomedical Research Centre.
Published: 2019

5. 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

6. 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, Gudnason 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., Hernandez Maria del C. Valdes, Luciano Michelle, Liewald David, Deary Ian J., Starr John M., Bastin Mark E., Maniega Susana Munoz, 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 Andre G., van der Lugt Aad, Wittfeld Katharina, Grabe Hans J., Hosten Norbert, von Sarnowski Bettina, Voelker 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, Thanh Phan, 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 Stephanie, 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, Gudnason 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., Hernandez Maria del C. Valdes, Luciano Michelle, Liewald David, Deary Ian J., Starr John M., Bastin Mark E., Maniega Susana Munoz, 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 Andre G., van der Lugt Aad, Wittfeld Katharina, Grabe Hans J., Hosten Norbert, von Sarnowski Bettina, Voelker 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, Thanh Phan, 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., and Debette Stephanie
Published: 2019

7. Impact of ADCY9 Genotype on Response to Anacetrapib.

Author: Hopewell, Jemma C., Ibrahim, Maysson, Hill, Michael, Shaw, Peter M., Braunwald, Eugene, Blaustein, Robert O., Bowman, Louise, Landray, Martin J., Sabatine, Marc S., and Collins, Rory
Subjects: *CHOLESTERYL ester transfer protein, *MYOCARDIAL infarction, *STROKE, *CLINICAL trial registries, *PROPORTIONAL hazards models, *GENOTYPES
Abstract: Supplemental Digital Content is available in the text. Background: Exploratory analyses of previous randomized trials generated a hypothesis that the clinical response to cholesteryl ester transfer protein (CETP) inhibitor therapy differs by ADCY9 genotype, prompting the ongoing dal-GenE trial in individuals with a particular genetic profile. The randomized placebo-controlled REVEAL trial (Randomized Evaluation of the Effects of Anacetrapib through Lipid-Modification) demonstrated the clinical efficacy of the CETP inhibitor anacetrapib among patients with preexisting atherosclerotic vascular disease. In the present study, we examined the impact of ADCY9 genotype on response to anacetrapib in the REVEAL trial. Methods: Individuals with stable atherosclerotic vascular disease who were treated with intensive atorvastatin therapy received either anacetrapib 100 mg daily or matching placebo. Cox proportional hazards models, adjusted for the first 5 principal components of ancestry, were used to estimate the effects of allocation to anacetrapib on major vascular events (a composite of coronary death, myocardial infarction, coronary revascularization, or presumed ischemic stroke) and the interaction with ADCY9 rs1967309 genotype. Results: Among 19 210 genotyped individuals of European ancestry, 2504 (13.0%) had a first major vascular event during 4 years median follow-up: 1216 (12.6%) among anacetrapib-allocated participants and 1288 (13.4%) among placebo-allocated participants. Proportional reductions in the risk of major vascular events with anacetrapib did not differ significantly by ADCY9 genotype: hazard ratio (HR) = 0.92 (95% CI, 0.81–1.05) for GG; HR = 0.94 (95% CI, 0.84–1.06) for AG; and HR = 0.93 (95% CI, 0.76–1.13) for AA genotype carriers, respectively; genotypic P for interaction = 0.96. Furthermore, there were no associations between ADCY9 genotype and the proportional reductions in the separate components of major vascular events or meaningful differences in lipid response to anacetrapib. Conclusions: The REVEAL trial is the single largest study to date evaluating the ADCY9 pharmacogenetic interaction. It provides no support for the hypothesis that ADCY9 genotype is materially relevant to the clinical effects of the CETP inhibitor anacetrapib. The ongoing dal-GenE study will provide direct evidence as to whether there is any specific pharmacogenetic interaction with dalcetrapib. Clinical Trial Registration: URL: https://www.clinicaltrials.gov. Unique identifier: NCT01252953. URL: http://www.isrctn.com. Unique identifier: ISRCTN48678192. URL: https://www.clinicaltrialsregister.eu. Unique identifier: 2010-023467-18. [ABSTRACT FROM AUTHOR]
Published: 2019
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8. Genetically Determined Levels of Circulating Cytokines and Risk of Stroke.

Author: Malik, Rainer, Bernhagen, Jürgen, Dichgans, Martin, Georgakis, Marios K., Kamatani, Yoichiro, Hopewell, Jemma C., Worrall, Bradford B., Gill, Dipender, Sudlow, Cathie L. M., Rannikmäe, Kristiina, Traylor, Matthew, Anderson, Christopher D., and Lee, Jin-Moo
Published: 2019
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9. Lp(a) (Lipoprotein[a]), an Exemplar for Precision Medicine: Insights From UK Biobank.

Author: Hopewell, Jemma C., Clarke, Robert, and Watkins, Hugh
Published: 2021
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10. Impact of Apolipoprotein(a) Isoform Size on Lipoprotein(a) Lowering in the HPS2-THRIVE Study.

Author: Parish, Sarah, Hopewell, Jemma C., Hill, Michael R., Marcovina, Santica, Valdes-Marquez, Elsa, Haynes, Richard, Offer, Alison, Pedersen, Terje R., Baigent, Colin, Collins, Rory, Landray, Martin, and Armitage, Jane
Abstract: BACKGROUND: Genetic studies have shown lipoprotein(a) (Lp[a]) to be an important causal risk factor for coronary disease. Apolipoprotein(a) isoform size is the chief determinant of Lp(a) levels, but its impact on the benefits of therapies that lower Lp(a) remains unclear. METHODS: HPS2-THRIVE (Heart Protection Study 2–Treatment of HDL to Reduce the Incidence of Vascular Events) is a randomized trial of niacin–laropiprant versus placebo on a background of simvastatin therapy. Plasma Lp(a) levels at baseline and 1 year post-randomization were measured in 3978 participants from the United Kingdom and China. Apolipoprotein(a) isoform size, estimated by the number of kringle IV domains, was measured by agarose gel electrophoresis and the predominantly expressed isoform identified. RESULTS: Allocation to niacin–laropiprant reduced mean Lp(a) by 12 (SE, 1) nmol/L overall and 34 (6) nmol/L in the top quintile by baseline Lp(a) level (Lp[a] ≥128 nmol/L). The mean proportional reduction in Lp(a) with niacin–laropiprant was 31% but varied strongly with predominant apolipoprotein(a) isoform size (PTrend=4×10−29) and was only 18% in the quintile with the highest baseline Lp(a) level and low isoform size. Estimates from genetic studies suggest that these Lp(a) reductions during the short term of the trial might yield proportional reductions in coronary risk of ≈2% overall and 6% in the top quintile by Lp(a) levels. CONCLUSIONS: Proportional reductions in Lp(a) were dependent on apolipoprotein(a) isoform size. Taking this into account, the likely benefits of niacin–laropiprant on coronary risk through Lp(a) lowering are small. Novel therapies that reduce high Lp(a) levels by at least 80 nmol/L (≈40%) may be needed to produce worthwhile benefits in people at the highest risk because of Lp(a). [ABSTRACT FROM AUTHOR]
Published: 2018
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11. Effects of Vascular and Nonvascular Adverse Events and of Extended-Release Niacin With Laropiprant on Health and Healthcare Costs.

Author: Kent, Seamus, Haynes, Richard, Hopewell, Jemma C., Parish, Sarah, Gray, Alastair, Landray, Martin J., Collins, Rory, Armitage, Jane, Mihaylova, Borislava, and HPS2-THRIVE Collaborative Group
Subjects: CARDIOVASCULAR disease prevention, DRUG therapy for hyperlipidemia, ANTILIPEMIC agents, CARDIOVASCULAR diseases, COMBINATION drug therapy, COMPARATIVE studies, CONTROLLED release preparations, COST effectiveness, HOSPITAL costs, HYPERLIPIDEMIA, LIPIDS, RESEARCH methodology, MEDICAL care costs, MEDICAL cooperation, NIACIN, QUALITY of life, RESEARCH, RESEARCH funding, TIME, EVALUATION research, RANDOMIZED controlled trials, TREATMENT effectiveness, DISEASE incidence, QUALITY-adjusted life years, INDOLE compounds, THERAPEUTICS
Abstract: Background: Extended-release niacin with laropiprant did not significantly reduce the risk of major vascular events and increased the risk of serious adverse events in Heart Protection Study 2-Treatment of HDL to Reduce the Incidence of Vascular Events (HPS2-THRIVE), but its net effects on health and healthcare costs are unknown.Methods and Results: 25 673 participants aged 50 to 80 years with previous cardiovascular disease were randomized to 2 g of extended-release niacin with 40 mg of laropiprant daily versus matching placebo, in addition to effective statin-based low-density lipoprotein cholesterol-lowering treatment. The net effects of niacin-laropiprant on quality-adjusted life years and hospital care costs (2012 UK £; converted into US $ using purchasing power parity index) during 4 years in HPS2-THRIVE were evaluated using estimates of the impact of serious adverse events on health-related quality of life and hospital care costs. During the study, participants assigned niacin-laropiprant experienced marginally but not statistically significantly lower survival (0.012 fewer years [standard error (SE) 0.007]), fewer quality-adjusted life years (0.023 [SE 0.007] fewer using UK EQ-5D scores; 0.020 [SE 0.006] fewer using US EQ-5D scores) and accrued greater hospital costs (UK £101 [SE £37]; US $145 [SE $53]). Stroke, heart failure, musculoskeletal events, gastrointestinal events, and infections were associated with significant decreases in health-related quality of life in both the year of the event and in subsequent years. All serious vascular and nonvascular events were associated with substantial increases in hospital care costs.Conclusions: In HPS2-THRIVE, the addition of extended-release niacin-laropiprant to statin-based therapy reduced quality of life-adjusted survival and increased hospital costs.Clinical Trial Registration: URL: http://clinicaltrials.gov. Unique identifier: NCT00461630. [ABSTRACT FROM AUTHOR]
Published: 2016
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12. Emerging Risk Factors for Stroke: What Have We Learned From Mendelian Randomization Studies?

Author: Hopewell, Jemma C. and Clarke, Robert
Published: 2016
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13. Low-frequency and common genetic variation in ischemic stroke: The METASTROKE collaboration.

Author: Malik, Rainer, Traylor, Matthew, Pulit, Sara L., Bevan, Steve, Hopewell, Jemma C., Holliday, Elizabeth G., Wei Zhao, Abrantes, Patricia, Amouyel, Philippe, Attia, John R., Battey, Thomas W. K., Berger, Klaus, Boncoraglio, Giorgio B., Chauhan, Ganesh, Yu-Ching Cheng, Wei-Min Chen, Clarke, Robert, Cotlarciuc, Ioana, Debette, Stephanie, and Falcone, Guido J.
Published: 2016
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14. 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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15. Genetic Overlap Between Diagnostic Subtypes of Ischemic Stroke.

Author: Holliday, Elizabeth G., Traylor, Matthew, Malik, Rainer, Bevan, Steve, Falcone, Guido, Hopewell, Jemma C., Yu-Ching Cheng, Cotlarciuc, Ioana, Bis, Joshua C., Boerwinkle, Eric, Boncoraglio, Giorgio B., Clarke, Robert, Cole, John W., Fornage, Myriam, Furie, Karen L., Arfan Ikram, M., Jannes, Jim, Kittner, Steven J., Lincz, Fisa F., and Maguire, Jane M.
Published: 2015
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16. Pharmacogenomics of statin therapy.

Author: Hopewell, Jemma C., Reith, Christina, and Armitage, Jane
Published: 2014
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17. Lipids and Lipoproteins and Risk of Different Vascular Events in the MRC/BHF Heart Protection Study.

Author: Parish, Sarah, Offer, Alison, Clarke, Robert, Hopewell, Jemma C., Hill, Michael R., Otvos, James D., Armitage, Jane, and Collins, Rory
Published: 2012
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18. Lipoprotein(a) Genetic Variants Associated With Coronary and Peripheral Vascular Disease but Not With Stroke Risk in the Heart Protection Study.

Author: Hopewell, Jemma C., Clarke, Robert, Parish, Sarah, Armitage, Jane, Lathrop, Mark, Hager, Jorg, and Collins, Rory
Subjects: PERIPHERAL vascular diseases, CARDIOVASCULAR diseases, DISEASE risk factors, GENETIC polymorphisms, MEDICAL genetics
Abstract: The article discusses a research study on the relationship of 2 single-nucleotide polymorphisms (SNPs) at lipopreotin a (LPA) locus (rs3798220) and (rs10455872) to coronary disease risk and the levels of LPA. Examined were the LPA score of 12,236 subjects who have vascular disease, ischemic stroke and coronary disease. Results showed the strong association of LPA score with coronary disease with the odds ratio (OR) per variant allele at 1.19 at 95% caloric intake (CI). Conclusion indicated that LPA may affect atherothrombotic vacular disease.
Published: 2011
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19. Genome-Wide Association Study of Peripheral Artery Disease.

Author: van Zuydam NR, Stiby A, Abdalla M, Austin E, Dahlström EH, McLachlan S, Vlachopoulou E, Ahlqvist E, Di Liao C, Sandholm N, Forsblom C, Mahajan A, Robertson NR, Rayner NW, Lindholm E, Sinisalo J, Perola M, Kallio M, Weiss E, Price J, Paterson A, Klein B, Salomaa V, Palmer CNA, Groop PH, Groop L, McCarthy MI, de Andrade M, Morris AP, Hopewell JC, Colhoun HM, and Kullo IJ
Subjects: Female, Genome-Wide Association Study, Humans, Male, Peripheral Arterial Disease epidemiology, Genetic Predisposition to Disease, Peripheral Arterial Disease genetics, Polymorphism, Single Nucleotide
Abstract: Background: Peripheral artery disease (PAD) affects >200 million people worldwide and is associated with high mortality and morbidity. We sought to identify genomic variants associated with PAD overall and in the contexts of diabetes and smoking status., Methods: We identified genetic variants associated with PAD and then meta-analyzed with published summary statistics from the Million Veterans Program and UK Biobank to replicate their findings. Next, we ran stratified genome-wide association analysis in ever smokers, never smokers, individuals with diabetes, and individuals with no history of diabetes and corresponding interaction analyses, to identify variants that modify the risk of PAD by diabetic or smoking status., Results: We identified 5 genome-wide significant ( P association ≤5×10 -8 ) associations with PAD in 449 548 (N cases =12 086) individuals of European ancestry near LPA (lipoprotein [a]), CDKN2BAS1 (CDKN2B antisense RNA 1), SH2B3 (SH2B adaptor protein 3) - PTPN11 (protein tyrosine phosphatase non-receptor type 11), HDAC9 (histone deacetylase 9), and CHRNA3 (cholinergic receptor nicotinic alpha 3 subunit ) loci (which overlapped previously reported associations). Meta-analysis with variants previously associated with PAD showed that 18 of 19 published variants remained genome-wide significant. In individuals with diabetes, rs116405693 at the CCSER1 (coiled-coil serine rich protein 1 ) locus was associated with PAD (odds ratio [95% CI], 1.51 [1.32-1.74], P diabetes =2.5×10 -9 , P interactionwithdiabetes =5.3×10 -7 ). Furthermore, in smokers, rs12910984 at the CHRNA3 locus was associated with PAD (odds ratio [95% CI], 1.15 [1.11-1.19], P smokers =9.3×10 -10 , P interactionwithsmoking =3.9×10 -5 )., Conclusions: Our analyses confirm the published genetic associations with PAD and identify novel variants that may influence susceptibility to PAD in the context of diabetes or smoking status.
Published: 2021
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20. Relative effects of LDL-C on ischemic stroke and coronary disease: A Mendelian randomization study.

Author: Valdes-Marquez E, Parish S, Clarke R, Stari T, Worrall BB, and Hopewell JC
Subjects: Causality, Humans, Hydroxymethylglutaryl-CoA Reductase Inhibitors therapeutic use, Hyperlipidemias drug therapy, Hyperlipidemias genetics, Hypolipidemic Agents therapeutic use, Mendelian Randomization Analysis, Brain Ischemia epidemiology, Cholesterol, LDL blood, Coronary Disease epidemiology, Hyperlipidemias epidemiology, Stroke epidemiology
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., (Copyright © 2019 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Academy of Neurology.)
Published: 2019
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21. Genetic and lifestyle risk factors for MRI-defined brain infarcts in a population-based setting.

Author: Chauhan G, Adams HHH, Satizabal CL, Bis JC, Teumer A, Sargurupremraj M, Hofer E, Trompet S, Hilal S, Smith AV, Jian X, Malik R, Traylor M, Pulit SL, Amouyel P, Mazoyer B, Zhu YC, Kaffashian S, Schilling S, Beecham GW, Montine TJ, Schellenberg GD, Kjartansson O, Guðnason V, Knopman DS, Griswold ME, Windham BG, Gottesman RF, Mosley TH, Schmidt R, Saba Y, Schmidt H, Takeuchi F, Yamaguchi S, Nabika T, Kato N, Rajan KB, Aggarwal NT, De Jager PL, Evans DA, Psaty BM, Rotter JI, Rice K, Lopez OL, Liao J, Chen C, Cheng CY, Wong TY, Ikram MK, van der Lee SJ, Amin N, Chouraki V, DeStefano AL, Aparicio HJ, Romero JR, Maillard P, DeCarli C, Wardlaw JM, Hernández MDCV, Luciano M, Liewald D, Deary IJ, Starr JM, Bastin ME, Muñoz Maniega S, Slagboom PE, Beekman M, Deelen J, Uh HW, Lemmens R, Brodaty H, Wright MJ, Ames D, Boncoraglio GB, Hopewell JC, Beecham AH, Blanton SH, Wright CB, Sacco RL, Wen W, Thalamuthu A, Armstrong NJ, Chong E, Schofield PR, Kwok JB, van der Grond J, Stott DJ, Ford I, Jukema JW, Vernooij MW, Hofman A, Uitterlinden AG, van der Lugt A, Wittfeld K, Grabe HJ, Hosten N, von Sarnowski B, Völker U, Levi C, Jimenez-Conde J, Sharma P, Sudlow CLM, Rosand J, Woo D, Cole JW, Meschia JF, Slowik A, Thijs V, Lindgren A, Melander O, Grewal RP, Rundek T, Rexrode K, Rothwell PM, Arnett DK, Jern C, Johnson JA, Benavente OR, Wasssertheil-Smoller S, Lee JM, Wong Q, Mitchell BD, Rich SS, McArdle PF, Geerlings MI, van der Graaf Y, de Bakker PIW, Asselbergs FW, Srikanth V, Thomson R, McWhirter R, Moran C, Callisaya M, Phan T, Rutten-Jacobs LCA, Bevan S, Tzourio C, Mather KA, Sachdev PS, van Duijn CM, Worrall BB, Dichgans M, Kittner SJ, Markus HS, Ikram MA, Fornage M, Launer LJ, Seshadri S, Longstreth WT Jr, and Debette S
Abstract: Objective: To explore genetic and lifestyle risk factors of MRI-defined brain infarcts (BI) in large population-based cohorts., Methods: We performed meta-analyses of genome-wide association studies (GWAS) and examined associations of vascular risk factors and their genetic risk scores (GRS) with MRI-defined BI and a subset of BI, namely, small subcortical BI (SSBI), in 18 population-based cohorts (n = 20,949) from 5 ethnicities (3,726 with BI, 2,021 with SSBI). Top loci were followed up in 7 population-based cohorts (n = 6,862; 1,483 with BI, 630 with SBBI), and we tested associations with related phenotypes including ischemic stroke and pathologically defined BI., Results: The mean prevalence was 17.7% for BI and 10.5% for SSBI, steeply rising after age 65. Two loci showed genome-wide significant association with BI: FBN2, p = 1.77 × 10 -8 ; and LINC00539/ZDHHC20, p = 5.82 × 10 -9 . Both have been associated with blood pressure (BP)-related phenotypes, but did not replicate in the smaller follow-up sample or show associations with related phenotypes. Age- and sex-adjusted associations with BI and SSBI were observed for BP traits ( p value for BI, p [BI] = 9.38 × 10 -25 ; p [SSBI] = 5.23 × 10 -14 for hypertension), smoking ( p [BI] = 4.4 × 10 -10 ; p [SSBI] = 1.2 × 10 -4 ), diabetes ( p [BI] = 1.7 × 10 -8 ; p [SSBI] = 2.8 × 10 -3 ), previous cardiovascular disease ( p [BI] = 1.0 × 10 -18 ; p [SSBI] = 2.3 × 10 -7 ), stroke ( p [BI] = 3.9 × 10 -69 ; p [SSBI] = 3.2 × 10 -24 ), and MRI-defined white matter hyperintensity burden ( p [BI] = 1.43 × 10 -157 ; p [SSBI] = 3.16 × 10 -106 ), but not with body mass index or cholesterol. GRS of BP traits were associated with BI and SSBI ( p ≤ 0.0022), without indication of directional pleiotropy., Conclusion: In this multiethnic GWAS meta-analysis, including over 20,000 population-based participants, we identified genetic risk loci for BI requiring validation once additional large datasets become available. High BP, including genetically determined, was the most significant modifiable, causal risk factor for BI., (Copyright © 2019 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Academy of Neurology.)
Published: 2019
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22. Genetically Determined Levels of Circulating Cytokines and Risk of Stroke.

Author: Georgakis MK, Gill D, Rannikmäe K, Traylor M, Anderson CD, Lee JM, Kamatani Y, Hopewell JC, Worrall BB, Bernhagen J, Sudlow CLM, Malik R, and Dichgans M
Subjects: Case-Control Studies, Genetic Predisposition to Disease, Genome-Wide Association Study, Humans, Mendelian Randomization Analysis, Observational Studies as Topic, Phenotype, Risk Assessment, Risk Factors, Stroke diagnosis, Chemokine CCL2 blood, Chemokine CCL2 genetics, Polymorphism, Single Nucleotide, Stroke blood, Stroke genetics
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 2-sample Mendelian randomization (MR) study., Methods: Genetic instruments for 41 cytokines and growth factors were obtained from a genome-wide association study of 8293 healthy adults. Their associations with stroke and stroke subtypes were evaluated in the MEGASTROKE genome-wide association study data set (67 162 cases; 454 450 controls) applying inverse variance-weighted meta-analysis, weighted-median analysis, Mendelian randomization-Egger regression, and multivariable Mendelian randomization. The UK Biobank cohort was used as an independent validation sample (4985 cases; 364 434 controls). Genetic instruments for monocyte chemoattractant protein-1 (MCP-1/CCL2) were further tested for association with etiologically related vascular traits by using publicly available genome-wide association study data., Results: Genetic predisposition to higher MCP-1 levels was associated with higher risk of any stroke (odds ratio [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 patients with stroke in comparison with controls., Conclusions: Genetic predisposition to elevated circulating levels of MCP-1 is associated with higher risk of stroke, in particular 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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23. Impact of Apolipoprotein(a) Isoform Size on Lipoprotein(a) Lowering in the HPS2-THRIVE Study.

Author: Parish S, Hopewell JC, Hill MR, Marcovina S, Valdes-Marquez E, Haynes R, Offer A, Pedersen TR, Baigent C, Collins R, Landray M, and Armitage J
Subjects: Aged, Coronary Disease, Female, Humans, Male, Middle Aged, Risk Factors, Hypolipidemic Agents therapeutic use, Indoles therapeutic use, Lipoprotein(a) blood, Lipoprotein(a) chemistry, Niacin therapeutic use, Protein Isoforms, Simvastatin therapeutic use
Abstract: Background: Genetic studies have shown lipoprotein(a) (Lp[a]) to be an important causal risk factor for coronary disease. Apolipoprotein(a) isoform size is the chief determinant of Lp(a) levels, but its impact on the benefits of therapies that lower Lp(a) remains unclear., Methods: HPS2-THRIVE (Heart Protection Study 2-Treatment of HDL to Reduce the Incidence of Vascular Events) is a randomized trial of niacin-laropiprant versus placebo on a background of simvastatin therapy. Plasma Lp(a) levels at baseline and 1 year post-randomization were measured in 3978 participants from the United Kingdom and China. Apolipoprotein(a) isoform size, estimated by the number of kringle IV domains, was measured by agarose gel electrophoresis and the predominantly expressed isoform identified., Results: Allocation to niacin-laropiprant reduced mean Lp(a) by 12 (SE, 1) nmol/L overall and 34 (6) nmol/L in the top quintile by baseline Lp(a) level (Lp[a] ≥128 nmol/L). The mean proportional reduction in Lp(a) with niacin-laropiprant was 31% but varied strongly with predominant apolipoprotein(a) isoform size ( P Trend =4×10 -29 ) and was only 18% in the quintile with the highest baseline Lp(a) level and low isoform size. Estimates from genetic studies suggest that these Lp(a) reductions during the short term of the trial might yield proportional reductions in coronary risk of ≈2% overall and 6% in the top quintile by Lp(a) levels., Conclusions: Proportional reductions in Lp(a) were dependent on apolipoprotein(a) isoform size. Taking this into account, the likely benefits of niacin-laropiprant on coronary risk through Lp(a) lowering are small. Novel therapies that reduce high Lp(a) levels by at least 80 nmol/L (≈40%) may be needed to produce worthwhile benefits in people at the highest risk because of Lp(a)., Clinical Trial Registration: URL: https://clinicaltrials.gov. Unique identifier: NCT00461630., (© 2018 The Authors.)
Published: 2018
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24. Genome-Wide Association Analysis of Young-Onset Stroke Identifies a Locus on Chromosome 10q25 Near HABP2.

Author: Cheng YC, Stanne TM, Giese AK, Ho WK, Traylor M, Amouyel P, Holliday EG, Malik R, Xu H, Kittner SJ, Cole JW, O'Connell JR, Danesh J, Rasheed A, Zhao W, Engelter S, Grond-Ginsbach C, Kamatani Y, Lathrop M, Leys D, Thijs V, Metso TM, Tatlisumak T, Pezzini A, Parati EA, Norrving B, Bevan S, Rothwell PM, Sudlow C, Slowik A, Lindgren A, Walters MR, Jannes J, Shen J, Crosslin D, Doheny K, Laurie CC, Kanse SM, Bis JC, Fornage M, Mosley TH, Hopewell JC, Strauch K, Müller-Nurasyid M, Gieger C, Waldenberger M, Peters A, Meisinger C, Ikram MA, Longstreth WT Jr, Meschia JF, Seshadri S, Sharma P, Worrall B, Jern C, Levi C, Dichgans M, Boncoraglio GB, Markus HS, Debette S, Rolfs A, Saleheen D, and Mitchell BD
Subjects: Adult, Age of Onset, Aged, Asian People genetics, Black People genetics, Brain Ischemia complications, Chromosomes, Human, Pair 10, Computer Simulation, DNA, Intergenic genetics, Female, Genetic Predisposition to Disease, Genome-Wide Association Study, Humans, Male, Middle Aged, Odds Ratio, Polymorphism, Single Nucleotide, Serine Endopeptidases metabolism, Stroke etiology, White People genetics, Brain Ischemia genetics, Serine Endopeptidases genetics, Stroke genetics
Abstract: Background and Purpose: Although a genetic contribution to ischemic stroke is well recognized, only a handful of stroke loci have been identified by large-scale genetic association studies to date. Hypothesizing that genetic effects might be stronger for early- versus late-onset stroke, we conducted a 2-stage meta-analysis of genome-wide association studies, focusing on stroke cases with an age of onset <60 years., Methods: The discovery stage of our genome-wide association studies included 4505 cases and 21 968 controls of European, South-Asian, and African ancestry, drawn from 6 studies. In Stage 2, we selected the lead genetic variants at loci with association P<5×10(-6) and performed in silico association analyses in an independent sample of ≤1003 cases and 7745 controls., Results: One stroke susceptibility locus at 10q25 reached genome-wide significance in the combined analysis of all samples from the discovery and follow-up stages (rs11196288; odds ratio =1.41; P=9.5×10(-9)). The associated locus is in an intergenic region between TCF7L2 and HABP2. In a further analysis in an independent sample, we found that 2 single nucleotide polymorphisms in high linkage disequilibrium with rs11196288 were significantly associated with total plasma factor VII-activating protease levels, a product of HABP2., Conclusions: HABP2, which encodes an extracellular serine protease involved in coagulation, fibrinolysis, and inflammatory pathways, may be a genetic susceptibility locus for early-onset stroke., (© 2016 American Heart Association, Inc.)
Published: 2016
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25. A common LPA null allele associates with lower lipoprotein(a) levels and coronary artery disease risk.

Author: Kyriakou T, Seedorf U, Goel A, Hopewell JC, Clarke R, Watkins H, and Farrall M
Subjects: Alleles, Case-Control Studies, Electrophoresis, Agar Gel, Gene Frequency, Genetic Predisposition to Disease, Genotype, High-Throughput Screening Assays, Humans, Kringles, Protein Isoforms genetics, Quantitative Trait Loci, Risk Factors, Apoprotein(a) genetics, Coronary Artery Disease genetics, Polymorphism, Single Nucleotide
Abstract: Objective: Increased levels of lipoprotein(a) are a highly heritable risk factor for coronary artery disease (CAD). The genetic determinants of lipoprotein(a) levels are mainly because of genetic variation in the apolipoprotein(a) gene (LPA). We have tested the association of a relatively common null allele of LPA with lipoprotein(a) levels and CAD risk in a large case-control cohort. We have also examined how null allele genotyping complements apolipoprotein(a) isoform typing to refine the relationship between LPA isoform size and circulating lipoprotein(a) levels., Approach and Results: The LPA null allele (rs41272114) was genotyped in the PROCARDIS (Precocious Coronary Artery Disease) case-control cohort (4073 CAD cases and 4225 controls). Lipoprotein(a) levels were measured in 909 CAD cases and 922 controls; apolipoprotein(a) isoform size was estimated using sodium dodecyl sulfate-agarose gel electrophoresis and a high-throughput quantitative polymerase chain reaction-based method. Null carriers are common (null allele frequency, 3%) and have significantly lower circulating lipoprotein(a) levels (P=2.1×10(-10)) and reduced CAD risk (odds ratio, 0.79 [0.66-0.97]; P=0.023) compared with noncarriers. An additive allelic model of apolipoprotein(a) isoform size, refined by null allele genotype and quantitative polymerase chain reaction values, showed a sigmoid relationship with lipoprotein(a) levels, with baseline levels for longer isoform alleles and progressively higher levels of lipoprotein(a) for shorter isoform alleles., Conclusions: The LPA null allele (rs41272114) is associated with decreased circulating lipoprotein(a) levels and decreased CAD risk. Incorporating rs41272114 refined apolipoprotein(a) isoform size typing obtained by immunoblotting and quantitative polymerase chain reaction. A joint genomic and isoform analysis revealed details of the relationship between apolipoprotein(a) isoform size and circulating lipoprotein(a) level consistent with a threshold effect on lipoprotein secretion., (© 2014 American Heart Association, Inc.)
Published: 2014
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26. Meta-analysis in more than 17,900 cases of ischemic stroke reveals a novel association at 12q24.12.

Author: Kilarski LL, Achterberg S, Devan WJ, Traylor M, Malik R, Lindgren A, Pare G, Sharma P, Slowik A, Thijs V, Walters M, Worrall BB, Sale MM, Algra A, Kappelle LJ, Wijmenga C, Norrving B, Sandling JK, Rönnblom L, Goris A, Franke A, Sudlow C, Rothwell PM, Levi C, Holliday EG, Fornage M, Psaty B, Gretarsdottir S, Thorsteinsdottir U, Seshadri S, Mitchell BD, Kittner S, Clarke R, Hopewell JC, Bis JC, Boncoraglio GB, Meschia J, Ikram MA, Hansen BM, Montaner J, Thorleifsson G, Stefanson K, Rosand J, de Bakker PI, Farrall M, Dichgans M, Markus HS, and Bevan S
Subjects: Cerebral Hemorrhage genetics, Genome-Wide Association Study, Genotype, Humans, Polymorphism, Single Nucleotide genetics, Risk, Stroke etiology, Brain Ischemia genetics, Chromosomes, Human, Pair 12 genetics, Genetic Predisposition to Disease, Stroke genetics
Abstract: Objectives: To perform a genome-wide association study (GWAS) using the Immunochip array in 3,420 cases of ischemic stroke and 6,821 controls, followed by a meta-analysis with data from more than 14,000 additional ischemic stroke cases., Methods: Using the Immunochip, we genotyped 3,420 ischemic stroke cases and 6,821 controls. After imputation we meta-analyzed the results with imputed GWAS data from 3,548 cases and 5,972 controls recruited from the ischemic stroke WTCCC2 study, and with summary statistics from a further 8,480 cases and 56,032 controls in the METASTROKE consortium. A final in silico "look-up" of 2 single nucleotide polymorphisms in 2,522 cases and 1,899 controls was performed. Associations were also examined in 1,088 cases with intracerebral hemorrhage and 1,102 controls., Results: In an overall analysis of 17,970 cases of ischemic stroke and 70,764 controls, we identified a novel association on chromosome 12q24 (rs10744777, odds ratio [OR] 1.10 [1.07-1.13], p = 7.12 × 10(-11)) with ischemic stroke. The association was with all ischemic stroke rather than an individual stroke subtype, with similar effect sizes seen in different stroke subtypes. There was no association with intracerebral hemorrhage (OR 1.03 [0.90-1.17], p = 0.695)., Conclusion: Our results show, for the first time, a genetic risk locus associated with ischemic stroke as a whole, rather than in a subtype-specific manner. This finding was not associated with intracerebral hemorrhage., (© 2014 American Academy of Neurology.)
Published: 2014
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27. Shared genetic susceptibility to ischemic stroke and coronary artery disease: a genome-wide analysis of common variants.

Author: Dichgans M, Malik R, König IR, Rosand J, Clarke R, Gretarsdottir S, Thorleifsson G, Mitchell BD, Assimes TL, Levi C, O'Donnell CJ, Fornage M, Thorsteinsdottir U, Psaty BM, Hengstenberg C, Seshadri S, Erdmann J, Bis JC, Peters A, Boncoraglio GB, März W, Meschia JF, Kathiresan S, Ikram MA, McPherson R, Stefansson K, Sudlow C, Reilly MP, Thompson JR, Sharma P, Hopewell JC, Chambers JC, Watkins H, Rothwell PM, Roberts R, Markus HS, Samani NJ, Farrall M, and Schunkert H
Subjects: Data Interpretation, Statistical, Genome-Wide Association Study, Humans, Phenotype, Polymorphism, Single Nucleotide, Reproducibility of Results, Risk Factors, Brain Ischemia epidemiology, Brain Ischemia genetics, Coronary Artery Disease epidemiology, Coronary Artery Disease genetics, Genetic Predisposition to Disease epidemiology, Stroke epidemiology, Stroke genetics
Abstract: Background and Purpose: Ischemic stroke (IS) and coronary artery disease (CAD) share several risk factors and each has a substantial heritability. We conducted a genome-wide analysis to evaluate the extent of shared genetic determination of the two diseases., Methods: Genome-wide association data were obtained from the METASTROKE, Coronary Artery Disease Genome-wide Replication and Meta-analysis (CARDIoGRAM), and Coronary Artery Disease (C4D) Genetics consortia. We first analyzed common variants reaching a nominal threshold of significance (P<0.01) for CAD for their association with IS and vice versa. We then examined specific overlap across phenotypes for variants that reached a high threshold of significance. Finally, we conducted a joint meta-analysis on the combined phenotype of IS or CAD. Corresponding analyses were performed restricted to the 2167 individuals with the ischemic large artery stroke (LAS) subtype., Results: Common variants associated with CAD at P<0.01 were associated with a significant excess risk for IS and for LAS and vice versa. Among the 42 known genome-wide significant loci for CAD, 3 and 5 loci were significantly associated with IS and LAS, respectively. In the joint meta-analyses, 15 loci passed genome-wide significance (P<5×10(-8)) for the combined phenotype of IS or CAD and 17 loci passed genome-wide significance for LAS or CAD. Because these loci had prior evidence for genome-wide significance for CAD, we specifically analyzed the respective signals for IS and LAS and found evidence for association at chr12q24/SH2B3 (PIS=1.62×10(-7)) and ABO (PIS=2.6×10(-4)), as well as at HDAC9 (PLAS=2.32×10(-12)), 9p21 (PLAS=3.70×10(-6)), RAI1-PEMT-RASD1 (PLAS=2.69×10(-5)), EDNRA (PLAS=7.29×10(-4)), and CYP17A1-CNNM2-NT5C2 (PLAS=4.9×10(-4))., Conclusions: Our results demonstrate substantial overlap in the genetic risk of IS and particularly the LAS subtype with CAD.
Published: 2014
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28. Multiethnic meta-analysis of genome-wide association studies in >100 000 subjects identifies 23 fibrinogen-associated Loci but no strong evidence of a causal association between circulating fibrinogen and cardiovascular disease.

Author: Sabater-Lleal M, Huang J, Chasman D, Naitza S, Dehghan A, Johnson AD, Teumer A, Reiner AP, Folkersen L, Basu S, Rudnicka AR, Trompet S, Mälarstig A, Baumert J, Bis JC, Guo X, Hottenga JJ, Shin SY, Lopez LM, Lahti J, Tanaka T, Yanek LR, Oudot-Mellakh T, Wilson JF, Navarro P, Huffman JE, Zemunik T, Redline S, Mehra R, Pulanic D, Rudan I, Wright AF, Kolcic I, Polasek O, Wild SH, Campbell H, Curb JD, Wallace R, Liu S, Eaton CB, Becker DM, Becker LC, Bandinelli S, Räikkönen K, Widen E, Palotie A, Fornage M, Green D, Gross M, Davies G, Harris SE, Liewald DC, Starr JM, Williams FM, Grant PJ, Spector TD, Strawbridge RJ, Silveira A, Sennblad B, Rivadeneira F, Uitterlinden AG, Franco OH, Hofman A, van Dongen J, Willemsen G, Boomsma DI, Yao J, Swords Jenny N, Haritunians T, McKnight B, Lumley T, Taylor KD, Rotter JI, Psaty BM, Peters A, Gieger C, Illig T, Grotevendt A, Homuth G, Völzke H, Kocher T, Goel A, Franzosi MG, Seedorf U, Clarke R, Steri M, Tarasov KV, Sanna S, Schlessinger D, Stott DJ, Sattar N, Buckley BM, Rumley A, Lowe GD, McArdle WL, Chen MH, Tofler GH, Song J, Boerwinkle E, Folsom AR, Rose LM, Franco-Cereceda A, Teichert M, Ikram MA, Mosley TH, Bevan S, Dichgans M, Rothwell PM, Sudlow CL, Hopewell JC, Chambers JC, Saleheen D, Kooner JS, Danesh J, Nelson CP, Erdmann J, Reilly MP, Kathiresan S, Schunkert H, Morange PE, Ferrucci L, Eriksson JG, Jacobs D, Deary IJ, Soranzo N, Witteman JC, de Geus EJ, Tracy RP, Hayward C, Koenig W, Cucca F, Jukema JW, Eriksson P, Seshadri S, Markus HS, Watkins H, Samani NJ, Wallaschofski H, Smith NL, Tregouet D, Ridker PM, Tang W, Strachan DP, Hamsten A, and O'Donnell CJ
Subjects: Adolescent, Adult, Aged, Aged, 80 and over, Black People genetics, Black People statistics & numerical data, Cardiovascular Diseases metabolism, Coronary Artery Disease ethnology, Coronary Artery Disease genetics, Coronary Artery Disease metabolism, Female, Genetic Predisposition to Disease ethnology, Hispanic or Latino genetics, Hispanic or Latino statistics & numerical data, Humans, Male, Middle Aged, Myocardial Infarction ethnology, Myocardial Infarction genetics, Myocardial Infarction metabolism, Polymorphism, Single Nucleotide genetics, Risk Factors, Stroke ethnology, Stroke genetics, Stroke metabolism, Venous Thromboembolism ethnology, Venous Thromboembolism genetics, Venous Thromboembolism metabolism, White People genetics, White People statistics & numerical data, Young Adult, Cardiovascular Diseases ethnology, Cardiovascular Diseases genetics, Fibrinogen genetics, Fibrinogen metabolism, Genetic Loci genetics, Genome-Wide Association Study
Abstract: Background: Estimates of the heritability of plasma fibrinogen concentration, an established predictor of cardiovascular disease, range from 34% to 50%. Genetic variants so far identified by genome-wide association studies explain only a small proportion (<2%) of its variation., Methods and Results: We conducted a meta-analysis of 28 genome-wide association studies including >90 000 subjects of European ancestry, the first genome-wide association meta-analysis of fibrinogen levels in 7 studies in blacks totaling 8289 samples, and a genome-wide association study in Hispanics totaling 1366 samples. Evaluation for association of single-nucleotide polymorphisms with clinical outcomes included a total of 40 695 cases and 85 582 controls for coronary artery disease, 4752 cases and 24 030 controls for stroke, and 3208 cases and 46 167 controls for venous thromboembolism. Overall, we identified 24 genome-wide significant (P<5×10(-8)) independent signals in 23 loci, including 15 novel associations, together accounting for 3.7% of plasma fibrinogen variation. Gene-set enrichment analysis highlighted key roles in fibrinogen regulation for the 3 structural fibrinogen genes and pathways related to inflammation, adipocytokines, and thyrotrophin-releasing hormone signaling. Whereas lead single-nucleotide polymorphisms in a few loci were significantly associated with coronary artery disease, the combined effect of all 24 fibrinogen-associated lead single-nucleotide polymorphisms was not significant for coronary artery disease, stroke, or venous thromboembolism., Conclusions: We identify 23 robustly associated fibrinogen loci, 15 of which are new. Clinical outcome analysis of these loci does not support a causal relationship between circulating levels of fibrinogen and coronary artery disease, stroke, or venous thromboembolism.
Published: 2013
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28 results on '"Hopewell, Jemma C."'

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20. Relative effects of LDL-C on ischemic stroke and coronary disease: A Mendelian randomization study.

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

22. Genetically Determined Levels of Circulating Cytokines and Risk of Stroke.

23. Impact of Apolipoprotein(a) Isoform Size on Lipoprotein(a) Lowering in the HPS2-THRIVE Study.

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28. Multiethnic meta-analysis of genome-wide association studies in >100 000 subjects identifies 23 fibrinogen-associated Loci but no strong evidence of a causal association between circulating fibrinogen and cardiovascular disease.

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