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Genome-wide meta-analysis of cerebral white matter hyperintensities in patients with stroke

2015; Lippincott Williams & Wilkins; Volume: 86; Issue: 2 Linguagem: Inglês

10.1212/wnl.0000000000002263

1526-632X

Matthew Traylor, Cathy R. Zhang, Poneh Adib‐Samii, William J. Devan, Owen Parsons, Silvia Lanfranconi, Sarah Gregory, Lisa Cloonan, Guido J. Falcone, Farid Radmanesh, Kaitlin Fitzpatrick, Allison Kanakis, Thomas R. Barrick, Barry Moynihan, Cathryn M. Lewis, Giorgio B. Boncoraglio, Robin Lemmens, Vincent Thijs, Cathie Sudlow, Joanna M. Wardlaw, Peter M. Rothwell, James F. Meschia, Bradford B. Worrall, Christopher Levi, Steve Bevan, Karen L. Furie, Martin Dichgans, Jonathan Rosand, Hugh S. Markus, Natalia S. Rost, Sylvia Smoller, John D. Sorkin, Xingwu Wang, Magdy Selim, Aleksandra Pikula, Philip A. Wolf, Stéphanie Debette, Sudha Seshadri, Paul I. W. de Bakker, Daniel I. Chasman, Kathryn M. Rexrode, Ida Chen, Jerome Rotter, May M. Luke, Michelle Sale, Tsong-Hai Lee, Ku‐Chou Chang, Mitchell S Elkind, Larry Goldstein, Michael L. James, Monique M.B. Breteler, Chris O’Donnell, Didier Leys, Cara L. Carty, Chelsea S. Kidwell, Jes Olesen, Pankaj Sharma, Stephen S. Rich, Turgot Tatlisumak, Olli Häppölä, Philippe Bijlenga, Carolina Soriano‐Tárraga, E. Giralt, Jaume Roquer, Jordi Jiménez‐Conde, Ioana Cotlarcius, John Hardy, Michał Korostyński, Giorgio B. Boncoraglio, Elena Ballabio, Eugenio Parati, Adamski Mateusz, Andrzej Urbanik, Tomasz Dziedzic, Jeremiasz Jagiełła, Jerzy Gąsowski, Marcin Wnuk, Rafał Olszanecki, Joanna Pera, Agnieszka Słowik, Karol Juchniewicz, Christopher Levi, Paul Nyquist, Íscia Lopes‐Cendes, Norberto L. Cabral, Paulo Henrique Condeixa de França, Anderson Gonçalves, Lina Keller, Milita Crisby, Konstantinos Kostulas, Robin Lemmens, Kourosh R. Ahmadi, Christian Opherk, Marco Duering, Martin Dichgans, Rainer Malik, Mariya Gonik, Julie Staals, Olle Melander, Philippe Burri, Ariane Sadr‐Nabavi, Javier Romero, Alessandro Biffi, Chris Anderson, Guido J. Falcone, Bart Brouwers, Jonathan Rosand, Natalia S. Rost, Rose Du, Christina Kourkoulis, Thomas W.K. Battey, Steven A. Lubitz, Bertram Müller‐Myhsok, James F. Meschia, Thomas G. Brott, Guillaume Paré, Alexander Pichler, Christian Enzinger, Helena Schmidt, Reinhold Schmidt, Stephan Seiler, Susan H. Blanton, Yoshiji Yamada, Anna Bersano, Tatjana Rundek, Ralph L. Sacco, Yu‐Feng Yvonne Chan, Andreas Gschwendtner, Zhen Sheng Deng, Taura L. Barr, Katrina Gwinn, Roderick A. Corriveau, Andrew B. Singleton, Salina P. Waddy, Lenore J. Launer, Christopher Chen, Kim En Le, Wei Ling Lee, Eng‐King Tan, Akintomi Olugbodi, Peter M. Rothwell, Sabrina Schilling, Vincent Mok, Elena R. Lebedeva, Christina Jern, Katarina Jood, Sandra Olsson, Helen Kim, Chaeyoung Lee, Laura L. Kilarski, Hugh S. Markus, Jennifer Peycke, Steve Bevan, Wayne H.-H. Sheu, Hung‐Yi Chiou, Joseph Chern, Elias A. Giraldo, Muhammad Taqi, Vivek Jain, Olivia Lam, George Howard, Daniel Woo, Steven J. Kittner, Braxton D. Mitchell, John W. Cole, Jeff O’Connell, Dianna M. Milewicz, Kachikwu Illoh, Bradford B. Worrall, Colin Stine, Bartosz Karaszewski, David J. Werring, Reecha Sofat, June Smalley, Cecilia M. Lindgren, Björn M. Hansen, Bo Norrving, Gustav Smith, Juan José Díaz, Vincent Thijs, Catharina J.M. Klijn, Femke van’t Hof, Ale Algra, Mary Joan MacLeod, Rodney T. Perry, Donna K. Arnett, Alessandro Pezzini, Alessandro Padovani, Steve Cramer, Mark Fisher, Danish Saleheen, Joseph P. Broderick, Brett Kissela, Alex S. F. Doney, Cathie Sudlow, Kristiina Rannikmäe, Scott Silliman, Caitrin W. McDonough, Matthew Walters, Annie Pedersén, Kazuma Nakagawa, Christy Chang, Mark Dobbins, Patrick McArdle, Yu-Ching Chang, R. Dale Brown, Devin L. Brown, Elizabeth Holliday, Raj N. Kalaria, Jane Maguire, John Attia, Martin Farrall, Anne‐Katrin Giese, Myriam Fornage, Jennifer J. Majersik, Mary Cushman, Keith L. Keene, Siiri Bennett, David Tirschwell, Bruce M. Psaty, Alex P. Reiner, W. T. Longstreth, David J. Spence, Joan Montaner, Israel Fernández‐Cadenas, Carl D. Langefeld, Cheryl Bushnell, Laura Heitsch, Jin‐Moo Lee, Kevin N. Sheth,

RNA modifications and cancer

Objective: For 3,670 stroke patients from the United Kingdom, United States, Australia, Belgium, and Italy, we performed a genome-wide meta-analysis of white matter hyperintensity volumes (WMHV) on data imputed to the 1000 Genomes reference dataset to provide insights into disease mechanisms. Methods: We first sought to identify genetic associations with white matter hyperintensities in a stroke population, and then examined whether genetic loci previously linked to WMHV in community populations are also associated in stroke patients. Having established that genetic associations are shared between the 2 populations, we performed a meta-analysis testing which associations with WMHV in stroke-free populations are associated overall when combined with stroke populations. Results: There were no associations at genome-wide significance with WMHV in stroke patients. All previously reported genome-wide significant associations with WMHV in community populations shared direction of effect in stroke patients. In a meta-analysis of the genome-wide significant and suggestive loci ( p < 5 × 10 −6 ) from community populations (15 single nucleotide polymorphisms in total) and from stroke patients, 6 independent loci were associated with WMHV in both populations. Four of these are novel associations at the genome-wide level (rs72934505 [ NBEAL1 ], p = 2.2 × 10 −8 ; rs941898 [ EVL ], p = 4.0 × 10 −8 ; rs962888 [ C1QL1 ], p = 1.1 × 10 −8 ; rs9515201 [ COL4A2 ], p = 6.9 × 10 −9 ). Conclusions: Genetic associations with WMHV are shared in otherwise healthy individuals and patients with stroke, indicating common genetic susceptibility in cerebral small vessel disease.