Association of Apolipoprotein E With Intracerebral Hemorrhage Risk by Race/Ethnicity A Meta-analysis


Por: Marini, S, Crawford, K, Morotti, A, Lee, MJ, Moomaw, CJ, Flaherty, ML, Giralt-Steinhauer, E, Elosua, R, Cuadrado-Godia, E, Soriano-Tarraga, C, Jagiella, JM, Hansen, BM, McCauley, JL, Tirschwell, DL, Brown, DL, Silliman, SL, Worrall, BB, Meschia, JF, Kidwell, CS, Testai, FD, Kittner, SJ, Deary, LJ, Samarasekera, N, Salman, RAS, Sudlow, CL, Klijn, CJM, van Nieuwenhuizen, KM, Delgado, P, Nonving, B, Lindgren, A, Goldstein, JN, Viswanathan, A, Greenberg, SM, Falcone, GJ, Langefeld, CD, Anderson, CD, Smoller, S, Sorkin, J, Wang, XW, Selim, M, Pikula, A, Wolf, P, Debette, S, Seshadri, S, de Bakker, P, Chasman, D, Rexrode, K, Chen, I, Rotter, J, Luke, M, Sale, M, Lee, TH, Chang, KC, Elkind, M, Goldstein, L, James, M, Breteler, M, O'Donnell, C, Leys, D, Carty, C, Kidwell, C, Olesen, J, Sharma, P, Rich, S, Tatlisumak, T, Happola, O, Bijlenga, P, Soriano, C, Giralt, E, Roquer, J, Jimenez-Conde, J, Cotlarcius, L, Hardy, J, Korostynski, M, Boncoraglio, G, Ballabio, E, Parati, E, Mateusz, A, Urbanik, A, Dziedzic, T, Jagiella, J, Gasowski, J, Wnuk, M, Olszanecki, R, Pera, J, Slowik, A, Juchniewicz, KJ, Levi, C, Nyquist, P, Cendes, I, Cabral, N, Franca, P, Goncalves, A, Keller, L, Crisby, M, Kostulas, K, Lennnnens, R, Ahmadi, K, Opherk, C, Duering, M, Dichgans, M, Malik, R, Gonik, M, Staals, J, Melander, O, Burri, P, Sadr-Nabavi, A, Romero, J, Biffi, A, Anderson, C, Falcone, G, Brouwers, B, Rosand, J, Rost, N, Du, R, Kourkoulis, C, Battey, T, Lubitz, S, Mueller-Myhsok, B, Meschia, J, Brott, T, Pare, G, Pichler, A, Enzinger, C, Schmidt, H, Schmidt, R, Seiler, S, Blanton, S, Yamada, Y, Bersano, A, Rundek, T, Sacco, R, Chan, YFY, Gschwendtner, A, Deng, Z, Barr, T, Gwinn, K, Corriveau, R, Singleton, A, Waddy, S, Launer, L, Chen, C, Le, KE, Lee, WL, Tan, EK, Olugbodi, A, Rothwell, P, Schilling, S, Mok, V, Lebedeva, E, Jem, C, Jood, K, Olsson, S, Kim, H, Lee, C, Kilarski, L, Markus, H, Peycke, J, Bevan, S, Sheu, W, Chiou, HY, Chern, J, Giraldo, E, Taqi, M, Jain, V, Lam, O, Howard, G, Woo, D, Kittner, S, Mitchell, B, Cole, J, O'Connell, J, Milewicz, D, Illoh, K, Worrall, B, Stine, C, Karaszewski, B, Werring, D, Sofat, R, Smalley, J, Lindgren, A, Hansen, B, Norrving, B, Smith, G, Martin, JJ, Thijs, V, Klijn, K, van't Hof, F, Algra, A, Macleod, M, Perry, R, Arnett, D, Pezzini, A, Padovani, A, Cramer, S, Fisher, M, Saleheen, D, Broderick, J, Kissela, B, Doney, A, Sudlow, C, Rannikmae, K, Silliman, S, McDonough, C, Walters, M, Pedersen, A, Nakagawa, K, Chang, C, Dobbins, M, McArdle, P, Chang, YC, Brown, R, Brown, D, Holliday, E, Kalaria, R, Maguire, J, Hunter, J, Attia, J, Farrall, M, Giese, AK, Fomage, M, Majersik, J, Cushman, M, Keene, K, Bennett, S, Tirschwell, D, Psaty, B, Reiner, A, Longstreth, W, Spence, D, Montaner, J, Fernandez-Cadenas, I, Langefeld, C, Bushnell, C, Heitsch, L, Lee, JM, Sheth, K, Int Genetics Consortium

Publicada: 1 abr 2019
Resumen:
IMPORTANCE Genetic studies of intracerebral hemorrhage (ICH) have focused mainly on white participants, but genetic risk may vary or could be concealed by differing nongenetic coexposures in nonwhite populations. Transethnic analysis of risk may clarify the role of genetics in ICH risk across populations. OBJECTIVE To evaluate associations between established differences in ICH risk by race/ethnicity and the variability in the risks of apolipoprotein E (APOE) epsilon 4 alleles, the most potent genetic risk factor for ICH. DESIGN, SETTING, AND PARTICIPANTS This case-control study of primary ICH meta-analyzed the association of APOE allele status on ICH risk, applying a 2-stage clustering approach based on race/ethnicity and stratified by a contributing study. A propensity score analysis was used to model the association of APOE with the burden of hypertension across race/ethnic groups. Primary ICH cases and controls were collected from 3 hospital- and population-based studies in the United States and 8 in European sites in the International Stroke Genetic Consortium. Participants were enrolled from January 1, 1999, to December 31, 2017. Participants with secondary causes of ICH were excluded from enrollment. Controls were regionally matched within each participating study. MAIN OUTCOMES AND MEASURES Clinical variables were systematically obtained from structured interviews within each site. APOE genotype was centrally determined for all studies. RESULTS In total, 13 124 participants (7153 [54.5%] male with a median [interquartile range] age of 66 [56-76] years) were included. In white participants, APOE epsilon 2 (odds ratio [OR], 1.49; 95% CI, 1.24-1.80; P < .001) and APOE epsilon 4 (OR, 1.51; 95% CI, 1.23-1.85; P < .001) were associated with lobar ICH risk; however, within self-identified Hispanic and black participants, no associations were found. After propensity score matching for hypertension burden, APOE epsilon 4 was associated with lobar ICH risk among Hispanic (OR, 1.14; 95% CI, 1.03-1.28; P = .01) but not in black (OR, 1.02; 95% CI, 0.98-1.07; P = .25) participants. APOE epsilon 2 and epsilon 4 did not show an association with nonlobar ICH risk in any race/ethnicity. CONCLUSIONS AND RELEVANCE APOE epsilon 4 and epsilon 2 alleles appear to affect lobar ICH risk variably by race/ethnicity, associations that are confirmed in white individuals but can be shown in Hispanic individuals only when the excess burden of hypertension is propensity score-matched; further studies are needed to explore the interactions between APOE alleles and environmental exposures that vary by race/ethnicity in representative populations at risk for ICH.

Filiaciones:
Marini, S:
 Massachusetts Gen Hosp, Ctr Genom Med, 185 Cambridge St CPZN 6818, Boston, MA 02114 USA

Crawford, K:
 Massachusetts Gen Hosp, Ctr Genom Med, 185 Cambridge St CPZN 6818, Boston, MA 02114 USA

Morotti, A:
 IRCCS Mondino Fdn, Stroke Unit, Pavia, Italy

Moomaw, CJ:
 Univ Cincinnati, Coll Med, Dept Neurol & Rehabil Med, Cincinnati, OH USA

Flaherty, ML:
 Univ Cincinnati, Coll Med, Dept Neurol & Rehabil Med, Cincinnati, OH USA

Giralt-Steinhauer, E:
 Univ Autonoma Barcelona, Inst Hosp del Mar Invest Med, Neurovasc Res Unit, Dept Neurol, Barcelona, Spain

Elosua, R:
 Univ Autonoma Barcelona, Inst Hosp del Mar Invest Med, Neurovasc Res Unit, Dept Neurol, Barcelona, Spain

Cuadrado-Godia, E:
 Univ Autonoma Barcelona, Inst Hosp del Mar Invest Med, Neurovasc Res Unit, Dept Neurol, Barcelona, Spain

Soriano-Tarraga, C:
 Univ Autonoma Barcelona, Inst Hosp del Mar Invest Med, Neurovasc Res Unit, Dept Neurol, Barcelona, Spain

Jagiella, JM:
 Jagiellonian Univ, Coll Med, Dept Neurol, Krakow, Poland

Hansen, BM:
 Lund Univ, Dept Clin Sci Lund, Neurol, Lund, Sweden

 Skane Univ Hosp, Dept Neurol & Rehabil, Lund, Sweden

McCauley, JL:
 Univ Miami, Miller Sch Med, John P Hussman Inst Human Genom, Miami, FL 33136 USA

Tirschwell, DL:
 Univ Washington, Harborview Med Ctr, Stroke Ctr, 325 9th Ave, Seattle, WA 98104 USA

Brown, DL:
 Univ Michigan, Cardiovasc Ctr, Ann Arbor, MI 48109 USA

Silliman, SL:
 Univ Florida, Coll Med, Dept Neurol, Gainesville, FL 32611 USA

Worrall, BB:
 Univ Virginia Hlth Syst, Dept Neurol & Publ Hlth Sci, Charlottesville, VA USA

Meschia, JF:
 Mayo Clin, Dept Neurol, Jacksonville, FL 32224 USA

Kidwell, CS:
 Univ Arizona, Dept Neurol, Tucson, AZ USA

Testai, FD:
 Univ Illinois, Coll Med, Dept Neurol & Rehabil, Chicago, IL USA

Kittner, SJ:
 Baltimore Vet Adm Med Ctr, Dept Neurol, Baltimore, MD USA

 Univ Maryland, Sch Med, Baltimore, MD 21201 USA

Deary, LJ:
 Univ Edinburgh, Ctr Cognit Ageing & Cognit Epidemiol, Edinburgh, Midlothian, Scotland

Samarasekera, N:
 Univ Edinburgh, Ctr Clin Brain Sci, Edinburgh, Midlothian, Scotland

Salman, RAS:
 Univ Edinburgh, Ctr Clin Brain Sci, Edinburgh, Midlothian, Scotland

Sudlow, CL:
 Univ Edinburgh, Usher Inst Populat Hlth Sci & Informat, Med Informat Ctr, Edinburgh, Midlothian, Scotland

Klijn, CJM:
 Radboud Univ Nijmegen, Med Ctr, Donders Inst Brain Cognit & Behav, Dept Neurol, Nijmegen, Netherlands

 Univ Med Ctr Utrecht, Brain Ctr Rudolf Magnus, Dept Neurol & Neurosurg, Utrecht, Netherlands

van Nieuwenhuizen, KM:
 Radboud Univ Nijmegen, Med Ctr, Donders Inst Brain Cognit & Behav, Dept Neurol, Nijmegen, Netherlands

 Univ Med Ctr Utrecht, Brain Ctr Rudolf Magnus, Dept Neurol & Neurosurg, Utrecht, Netherlands

Delgado, P:
 Univ Autonoma Barcelona, Hosp Vall dHebron, Inst Recerca, Neurovasc Res Lab, Barcelona, Spain

 Univ Autonoma Barcelona, Hosp Vall dHebron, Inst Recerca, Neurovasc Unit, Barcelona, Spain

Lindgren, A:
 Lund Univ, Dept Clin Sci Lund, Neurol, Lund, Sweden

 Skane Univ Hosp, Dept Neurol & Rehabil, Lund, Sweden

 Univ Hosp Lund, Steering Comm, Sci Comm, Lund, Sweden

Goldstein, JN:
 Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA

Viswanathan, A:
 Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA

Greenberg, SM:
 Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA

Falcone, GJ:
 Yale Univ, Sch Med, Dept Neurol, Div Neurocrit Care & Emergency Neurol, New Haven, CT 06510 USA

 Yale Univ, Yale Sch Med, Ctr Neuroepidemiol & Clin Neurol Res, New Haven, CT USA

Langefeld, CD:
 Wake Forest Univ, Ctr Publ Hlth Genom, Winston Salem, NC 27109 USA

 Wake Forest Univ, Dept Biostat Sci, Winston Salem, NC 27109 USA

Anderson, CD:
 Massachusetts Gen Hosp, Ctr Genom Med, 185 Cambridge St CPZN 6818, Boston, MA 02114 USA

 Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA

 Broad Inst, Program Med & Populat Genet, Cambridge, MA USA

Smoller, S:
 Albert Einstein Coll Med, Bronx, NY 10467 USA

Sorkin, J:
 Baltimore VA Med Ctr, Baltimore, MD USA

Wang, XW:
 Beijing Hypertens League Inst, Beijing, Peoples R China

Selim, M:
 Beth Israel Deaconess Med Ctr, Dept Neurol, Stroke Div, Boston, MA 02215 USA

 Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA

Pikula, A:
 Boston Univ, Med Ctr, Boston, MA 02215 USA

Wolf, P:
 Boston Univ, Sch Med, Boston, MA 02215 USA

Debette, S:
 Boston Univ, Sch Med, Boston, MA 02215 USA

Seshadri, S:
 Boston Univ, Sch Med, Boston, MA 02215 USA

de Bakker, P:
 Brigham & Womens Hosp, Boston, MA 02115 USA

Chasman, D:
 Brigham & Womens Hosp, Boston, MA 02115 USA

Rexrode, K:
 Harvard Med Sch, Brigham & Womens Hosp, Boston, MA 02115 USA

Chen, I:
 Cedars Sinai Med Ctr, Los Angeles, CA 90048 USA

Rotter, J:
 Cedars Sinai Med Ctr, Los Angeles, CA 90048 USA

Luke, M:
 Celera, Alameda, CA USA

Sale, M:
 Univ Virginia, Charlottesville, VA 22903 USA

Lee, TH:
 Chang Gung Mem Hosp, Linkou Med Ctr, Taoyuan, Taiwan

Chang, KC:
 Chang Gung Mem Hosp, Taoyuan, Taiwan

 Chang Gung Univ, Coll Med, Taoyuan, Taiwan

Elkind, M:
 Columbia Univ, New York, NY 10027 USA

Goldstein, L:
 Duke Univ, Durham, NC 27706 USA

James, M:
 Duke Univ, Durham, NC 27706 USA

Breteler, M:
 Erasmus Univ, Rotterdam, Netherlands

O'Donnell, C:
 Framingham Heart Dis Epidemiol Study, Framingham, MA USA

Carty, C:
 Fred Hutchinson Canc Res Ctr, 1124 Columbia St, Seattle, WA 98104 USA

Kidwell, C:
 Univ Arizona, Dept Neurol, Tucson, AZ USA

 Georgetown Univ, Washington, DC 20057 USA

Olesen, J:
 Glostrup Cty Hosp, Glostrup, Denmark

Sharma, P:
 Hammersmith Hosp, London, England

 Imperial Coll London, London, England

Rich, S:
 Univ Virginia Hlth Syst, Charlottesville, VA USA

Tatlisumak, T:
 Univ Helsinki, Cent Hosp, Helsinki, Finland

Happola, O:
 Univ Helsinki, Cent Hosp, Helsinki, Finland

Bijlenga, P:
 Hop Univ Geneve, Geneva, Switzerland

Soriano, C:
 Hosp del Mar, IMIM, Barcelona, Spain

Roquer, J:
 Univ Autonoma Barcelona, Inst Hosp del Mar Invest Med, Neurovasc Res Unit, Dept Neurol, Barcelona, Spain

 Hosp del Mar, IMIM, Barcelona, Spain

Jimenez-Conde, J:
 Univ Autonoma Barcelona, Inst Hosp del Mar Invest Med, Neurovasc Res Unit, Dept Neurol, Barcelona, Spain

 Hosp del Mar, IMIM, Barcelona, Spain

Cotlarcius, L:
 Imperial Coll London, London, England

Hardy, J:
 UCL, Inst Neurol, London, England

Korostynski, M:
 Inst Pharmacol, Krakow, Poland

Boncoraglio, G:
 IRCCS Ist Neurol Carlo Besta, Milan, Italy

Ballabio, E:
 IRCCS Ist Neurol Carlo Besta, Milan, Italy

Parati, E:
 IRCCS Ist Neurol Carlo Besta, Milan, Italy

Mateusz, A:
 Jagiellonian Univ, Krakow, Poland

Urbanik, A:
 Jagiellonian Univ, Coll Med, Dept Neurol, Krakow, Poland

 Jagiellonian Univ, Krakow, Poland

Dziedzic, T:
 Jagiellonian Univ, Krakow, Poland

Jagiella, J:
 Jagiellonian Univ, Coll Med, Dept Neurol, Krakow, Poland

 Jagiellonian Univ, Krakow, Poland

Gasowski, J:
 Jagiellonian Univ, Krakow, Poland

Wnuk, M:
 Jagiellonian Univ, Krakow, Poland

Olszanecki, R:
 Jagiellonian Univ, Krakow, Poland

Pera, J:
 Jagiellonian Univ, Coll Med, Dept Neurol, Krakow, Poland

 Jagiellonian Univ, Krakow, Poland

Slowik, A:
 Jagiellonian Univ, Coll Med, Dept Neurol, Krakow, Poland

 Jagiellonian Univ, Krakow, Poland

Juchniewicz, KJ:
 Jagiellonian Univ, Krakow, Poland

Levi, C:
 Univ Newcastle, John Hunter Hosp, Callaghan, NSW 2308, Australia

Nyquist, P:
 Johns Hopkins Sch Med, Sci Comm, Baltimore, MD USA

Cendes, I:
 Joinville Biobank, Joinville, SC, Brazil

Cabral, N:
 Joinville Biobank, Joinville, SC, Brazil

Franca, P:
 Joinville Biobank, Joinville, SC, Brazil

Goncalves, A:
 Joinville Biobank, Joinville, SC, Brazil

Keller, L:
 Karolinska Inst, Stockholm, Sweden

Crisby, M:
 Karolinska Inst, Stockholm, Sweden

Kostulas, K:
 Karolinska Inst, Stockholm, Sweden

 Karolinska Univ Hosp, Huddinge Unit, Huddinge, Sweden

Lennnnens, R:
 KULeuven, Leuven, Belgium

Opherk, C:
 Ludwig Maxinnilians Univ Munchen, Munich, Germany

Duering, M:
 Ludwig Maxinnilians Univ Munchen, Munich, Germany

Dichgans, M:
 Ludwig Maxinnilians Univ Munchen, Munich, Germany

Malik, R:
 Ludwig Maxinnilians Univ Munchen, Munich, Germany

Gonik, M:
 Ludwig Maxinnilians Univ Munchen, Munich, Germany

Staals, J:
 Maastricht Univ, Med Ctr, Maastricht, Netherlands

Melander, O:
 Malmo Univ Hosp, Lund, Sweden

Burri, P:
 Malmo Univ Hosp, Lund, Sweden

Sadr-Nabavi, A:
 Mashhad Univ Med Sci, Mashhad, Razavi Khorasan, Iran

Romero, J:
 Massachusetts Gen Hosp, Boston, MA 02114 USA

Biffi, A:
 Massachusetts Gen Hosp, Div Behav Neurol, Boston, MA 02114 USA

 Massachusetts Gen Hosp, Boston, MA 02114 USA

Anderson, C:
 Massachusetts Gen Hosp, Ctr Genom Med, 185 Cambridge St CPZN 6818, Boston, MA 02114 USA

 Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA

 Broad Inst, Program Med & Populat Genet, Cambridge, MA USA

 Massachusetts Gen Hosp, Boston, MA 02114 USA

Falcone, G:
 Yale Univ, Sch Med, Dept Neurol, Div Neurocrit Care & Emergency Neurol, New Haven, CT 06510 USA

 Yale Univ, Yale Sch Med, Ctr Neuroepidemiol & Clin Neurol Res, New Haven, CT USA

 Massachusetts Gen Hosp, Boston, MA 02114 USA

Brouwers, B:
 Massachusetts Gen Hosp, Boston, MA 02114 USA

Rosand, J:
 Massachusetts Gen Hosp, Ctr Genom Med, 185 Cambridge St CPZN 6818, Boston, MA 02114 USA

 Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA

 Broad Inst, Program Med & Populat Genet, Cambridge, MA USA

 Massachusetts Gen Hosp, Boston, MA 02114 USA

Rost, N:
 Massachusetts Gen Hosp, Boston, MA 02114 USA

Du, R:
 Massachusetts Gen Hosp, Boston, MA 02114 USA

Kourkoulis, C:
 Massachusetts Gen Hosp, Boston, MA 02114 USA

Battey, T:
 Massachusetts Gen Hosp, Boston, MA 02114 USA

Lubitz, S:
 Massachusetts Gen Hosp, Boston, MA 02114 USA

Mueller-Myhsok, B:
 Max Planck Inst Psychiat, Munich, Germany

Meschia, J:
 Mayo Clin, Dept Neurol, Jacksonville, FL 32224 USA

 Mayo Clin, Steering Comm, Rochester, MN USA

Brott, T:
 Mayo Clin, Rochester, MN USA

Pare, G:
 McMaster Univ, Steering Comm, Sci Comm, Hamilton, ON, Canada

Pichler, A:
 Jagiellonian Univ, Coll Med, Dept Neurol, Krakow, Poland

 Med Univ Graz, Graz, Austria

Enzinger, C:
 Med Univ Graz, Dept Neurol, Graz, Austria

 Med Univ Graz, Graz, Austria

Schmidt, H:
 Med Univ Graz, Graz, Austria

Schmidt, R:
 Med Univ Graz, Dept Neurol, Graz, Austria

 Med Univ Graz, Graz, Austria

Seiler, S:
 Med Univ Graz, Graz, Austria

Blanton, S:
 Univ Miami, Miller Sch Med, Miami Inst Human Genom, Miami, FL 33136 USA

Yamada, Y:
 Mie Univ, Tsu, Mie, Japan

Bersano, A:
 Milan Univ, Milan, Italy

Rundek, T:
 Univ Miami, Coral Gables, FL 33124 USA

Sacco, R:
 Univ Miami, Coral Gables, FL 33124 USA

Chan, YFY:
 Mt Sinai Med Ctr, New York, NY 10029 USA

Gschwendtner, A:
 Ludwig Maximilians Univ Munchen, Munich, Germany

Deng, Z:
 Southern Med Univ, Nanfang Hosp, Guangzhou, Guangdong, Peoples R China

Barr, T:
 NIH, Bethesda, MD USA

Gwinn, K:
 NIH, Bethesda, MD USA

Corriveau, R:
 NIH, Bethesda, MD USA

Singleton, A:
 NIH, Bethesda, MD USA

Waddy, S:
 NIH, Bethesda, MD USA

Launer, L:
 NIH, Bethesda, MD USA

Chen, C:
 Singapore Gen Hosp, Natl Neurosci Inst, Singapore, Singapore

Le, KE:
 Singapore Gen Hosp, Natl Neurosci Inst, Singapore, Singapore

Lee, WL:
 Singapore Gen Hosp, Natl Neurosci Inst, Singapore, Singapore

Tan, EK:
 Singapore Gen Hosp, Natl Neurosci Inst, Singapore, Singapore

Olugbodi, A:
 Obafemi Awolowo Univ, Ife, Nigeria

Rothwell, P:
 Radcliffe Infirm, Oxford, England

Mok, V:
 Chinese Univ Hong Kong, Prince Wales Hosp, Hong Kong, Peoples R China

Jem, C:
 Sahlgrens Univ Hosp, Sci Comm, Gothenburg, Sweden

Jood, K:
 Sahlgrens Univ Hosp, Gothenburg, Sweden

Olsson, S:
 Sahlgrens Univ Hosp, Gothenburg, Sweden

Kim, H:
 San Francisco Gen Hosp, San Francisco, CA 94110 USA

 Ctr Cerebrovasc Res, San Francisco, CA USA

Lee, C:
 Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA

 Soongsil Univ, Seoul, South Korea

Kilarski, L:
 St Georges Univ London, London, England

Markus, H:
 St Georges Univ London, London, England

Peycke, J:
 St Georges Univ London, London, England

Bevan, S:
 St Georges Univ London, London, England

Sheu, W:
 Taichung Vet Gen Hosp, Taichung, Taiwan

Chiou, HY:
 Taipei Med Univ, Taipei, Taiwan

Chern, J:
 Taipei Med Univ, Taipei, Taiwan

Giraldo, E:
 Univ Tennessee, Ctr Hlth Sci, Memphis, TN 38163 USA

Taqi, M:
 Univ Tennessee, Ctr Hlth Sci, Memphis, TN 38163 USA

Jain, V:
 UC Irvine, Med Ctr, Irvine, CA USA

Lam, O:
 Univ Calif San Francisco, San Francisco, CA 94143 USA

Howard, G:
 Univ Alabama, Sch Publ Hlth, Tuscaloosa, AL 35487 USA

Woo, D:
 Univ Cincinnati, Coll Med, Dept Neurol & Rehabil Med, Cincinnati, OH USA

 Univ Cincinnati, Steering Comm, Cincinnati, OH 45221 USA

Kittner, S:
 Baltimore Vet Adm Med Ctr, Dept Neurol, Baltimore, MD USA

 Univ Maryland, Sch Med, Baltimore, MD 21201 USA

 Univ Maryland Hosp, Baltimore, MD 21201 USA

Mitchell, B:
 Univ Maryland, Sch Med, Baltimore, MD 21201 USA

Cole, J:
 Univ Maryland, Sch Med, Baltimore, MD 21201 USA

O'Connell, J:
 Univ Maryland, Sch Med, Baltimore, MD 21201 USA

Milewicz, D:
 Univ Texas Med Sch, Houston, TX USA

Illoh, K:
 Univ Texas Houston, Houston, TX USA

Worrall, B:
 Univ Virginia Hlth Syst, Dept Neurol & Publ Hlth Sci, Charlottesville, VA USA

 Univ Virginia Hlth Syst, Charlottesville, VA USA

Stine, C:
 Univ Maryland, Sch Med, Baltimore, MD 21201 USA

Karaszewski, B:
 UCL, London, England

Werring, D:
 UCL, London, England

Sofat, R:
 UCL, London, England

Smalley, J:
 UCL, London, England

Lindgren, A:
 Lund Univ, Dept Clin Sci Lund, Neurol, Lund, Sweden

 Skane Univ Hosp, Dept Neurol & Rehabil, Lund, Sweden

 Univ Hosp Lund, Steering Comm, Sci Comm, Lund, Sweden

Hansen, B:
 Lund Univ, Dept Clin Sci Lund, Neurol, Lund, Sweden

 Skane Univ Hosp, Dept Neurol & Rehabil, Lund, Sweden

 Univ Hosp Lund, Lund, Sweden

Norrving, B:
 Lund Univ, Dept Clin Sci Lund, Neurol, Lund, Sweden

 Skane Univ Hosp, Dept Neurol & Rehabil, Lund, Sweden

 Univ Hosp Lund, Lund, Sweden

Smith, G:
 Univ Hosp Lund, Lund, Sweden

Martin, JJ:
 Univ Hosp Sanatorio Allende, Cordoba, Argentina

Thijs, V:
 Univ Hosp Leuven, Leuven, Belgium

Klijn, K:
 Univ Med Ctr Utrecht, Utrecht, Netherlands

van't Hof, F:
 Univ Med Ctr Utrecht, Utrecht, Netherlands

Algra, A:
 Univ Med Ctr Utrecht, Utrecht, Netherlands

Macleod, M:
 Univ Aberdeen, Aberdeen, Scotland

Perry, R:
 Univ Alabama Birmingham, Sch Publ Hlth, Birmingham, AL 35294 USA

Arnett, D:
 Univ Alabama Birmingham, Sch Publ Hlth, Birmingham, AL 35294 USA

Pezzini, A:
 Univ Brescia, Dept Clin & Expt Sci, Neurol Clin, Brescia, Italy

 Univ Brescia, Brescia, Italy

Padovani, A:
 Univ Brescia, Brescia, Italy

Cramer, S:
 Univ Calif Irvine, Irvine, CA 92717 USA

Fisher, M:
 Univ Calif Irvine, Irvine, CA 92717 USA

Saleheen, D:
 Univ Penn, Philadelphia, PA 19104 USA

Broderick, J:
 Univ Cincinnati, Cincinnati, OH 45221 USA

Kissela, B:
 Univ Cincinnati, Cincinnati, OH 45221 USA

Doney, A:
 Univ Dundee, Dundee, Scotland

Sudlow, C:
 Univ Edinburgh, Usher Inst Populat Hlth Sci & Informat, Med Informat Ctr, Edinburgh, Midlothian, Scotland

 Univ Edinburgh, Edinburgh, Midlothian, Scotland

 Western Gen Hosp, Steering Comm, Edinburgh, Midlothian, Scotland

Rannikmae, K:
 Univ Edinburgh, Ctr Clin Brain Sci, Edinburgh, Midlothian, Scotland

 Univ Edinburgh, Edinburgh, Midlothian, Scotland

 Western Gen Hosp, Steering Comm, Edinburgh, Midlothian, Scotland

Silliman, S:
 Univ Florida, Coll Med, Dept Neurol, Gainesville, FL 32611 USA

 Univ Florida, Gainesville, FL 32611 USA

McDonough, C:
 Univ Florida, Gainesville, FL 32611 USA

Walters, M:
 Univ Glasgow, Glasgow, Lanark, Scotland

Pedersen, A:
 Univ Gothenburg, Gothenburg, Sweden

Nakagawa, K:
 Univ Hawaii, Honolulu, HI 96822 USA

Chang, C:
 Univ Maryland, College Pk, MD 20742 USA

Dobbins, M:
 Univ Maryland, College Pk, MD 20742 USA

McArdle, P:
 Univ Maryland, College Pk, MD 20742 USA

Chang, YC:
 Univ Maryland, College Pk, MD 20742 USA

Brown, R:
 Univ Michigan, Ann Arbor, MI 48109 USA

Brown, D:
 Univ Michigan, Cardiovasc Ctr, Ann Arbor, MI 48109 USA

 Univ Michigan, Ann Arbor, MI 48109 USA

Holliday, E:
 Univ Newcastle, Callaghan, NSW, Australia

Kalaria, R:
 Univ Newcastle, Callaghan, NSW, Australia

Maguire, J:
 Univ Newcastle, Callaghan, NSW, Australia

 John Hunter Hosp, Steering Comm, New Lambton Hts, NSW, Australia

Attia, J:
 Univ Newcastle, Callaghan, NSW, Australia

 John Hunter Hosp, New Lambton Hts, NSW, Australia

Farrall, M:
 Univ Oxford, Oxford, England

 Wellcome Trust Ctr Human Genet, Oxford, England

Giese, AK:
 Univ Rostock, Rostock, Germany

Fomage, M:
 Univ Texas Hlth Sci Ctr Houston, Sci Comm, Houston, TX 77030 USA

Majersik, J:
 Univ Utah, Sci Comm, Salt Lake City, UT 84112 USA

Cushman, M:
 Univ Vermont, Burlington, VT 05405 USA

 Fletcher Allen Hlth Care, Burlington, VT USA

Keene, K:
 Univ Virginia, Charlottesville, VA 22903 USA

Bennett, S:
 Univ Washington, Seattle, WA 98195 USA

Tirschwell, D:
 Univ Washington, Harborview Med Ctr, Stroke Ctr, 325 9th Ave, Seattle, WA 98104 USA

 Univ Washington, Seattle, WA 98195 USA

Psaty, B:
 Univ Washington, Seattle, WA 98195 USA

Reiner, A:
 Univ Washington, Seattle, WA 98195 USA

Longstreth, W:
 Univ Washington, Seattle, WA 98195 USA

 Harborview Med Ctr, Seattle, WA USA

Spence, D:
 Univ Western Ontario, Robarts Res Inst, London, ON, Canada

Montaner, J:
 Univ Autonoma Barcelona, Hosp Vall dHebron, Inst Recerca, Neurovasc Res Lab, Barcelona, Spain

 Univ Autonoma Barcelona, Hosp Vall dHebron, Inst Recerca, Neurovasc Unit, Barcelona, Spain

 Univ Seville, CSIC, Hosp Univ Virgen del Rocio, Inst Biomed Seville,IBiS, Seville, Spain

 Hosp Univ Virgen Macarena, Dept Neurol, Seville, Spain

 Vall dHebron Hosp, Barcelona, Spain

Fernandez-Cadenas, I:
 Univ Autonoma Barcelona, Hosp Vall dHebron, Inst Recerca, Neurovasc Res Lab, Barcelona, Spain

 Univ Autonoma Barcelona, Hosp Vall dHebron, Inst Recerca, Neurovasc Unit, Barcelona, Spain

 Hosp Santa Creu & Sant Pau, St Pau Inst Res, Stroke Pharmacogen & Genet, Barcelona, Spain

 Vall dHebron Hosp, Steering Comm, Barcelona, Spain

Langefeld, C:
 Wake Forest Univ, Ctr Publ Hlth Genom, Winston Salem, NC 27109 USA

 Wake Forest Univ, Dept Biostat Sci, Winston Salem, NC 27109 USA

 Wake Forest Univ, Winston Salem, NC 27109 USA

Bushnell, C:
 Wake Forest Univ Hlth Sci, Winston Salem, NC USA

Heitsch, L:
 Washington Univ, St Louis, MO 63130 USA

Lee, JM:
 Washington Univ, St Louis, MO 63130 USA

Sheth, K:
 Yale Sch Med, Yale New Haven Hosp, New Haven, CT USA
ISSN: 21686149
Editorial
AMER MEDICAL ASSOC, 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA, Estados Unidos America
Tipo de documento: Article
Volumen: 76 Número: 4
Páginas: 480-491
WOS Id: 000463873600017
ID de PubMed: 30726504
imagen Green Published, Hybrid Gold

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