Genome-wide meta-analysis of cerebral white matter hyperintensities in patients with stroke
Year: 2015
Type: review
Study design: Observational Study
Abstract: 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.
Source: Neurology
Authors: Matthew Traylor, Cathy R. Zhang, Poneh Adib-Samii, William J. Devan, Owen E. 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 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 Rost, Sylvia Smoller, John Sorkin, Xingwu Wang, Magdy Selim, Aleksandra Pikula, Philip Wolf, Stephanie Debette, Sudha Seshadri, Paul de Bakker, Daniel Chasman, Kathryn Rexrode, Ida Chen, Jerome Rotter, May Luke, Michelle Sale, Tsong-Hai Lee, Ku-Chou Chang, Mitchell Elkind, Larry Goldstein, Michael (Luke) James, Monique Breteler, Chris O'Donnell, Didier Leys, Cara Carty, Chelsea Kidwell, Jes Olesen, Pankaj Sharma, Stephen Rich, Turgot Tatlisumak, Olli Happola, Philippe Bijlenga, Carolina Soriano, Eva Giralt, Jaume Roquer, Jordi Jimenez-Conde, Ioana Cotlarcius, John Hardy, Michal Korostynski, Giorgio Boncoraglio, Elena Ballabio, Eugenio Parati, Adamski Mateusz, Andrzej Urbanik, Tomasz Dziedzic, Jeremiasz Jagiella, Jerzy Gasowski, Marcin Wnuk, Rafał Olszanecki, Joanna Pera, Agnieszka Slowik, Karol Józef Juchniewicz, Christopher Levi, Paul Nyquist, Iscia Cendes, Norberto Cabral, Paulo Franca, Anderson Goncalves, Lina Keller, Milita Crisby, Konstantinos Kostulas, Robin Lemmens, Kourosh 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 Falcone, Bart Brouwers, Jonathan Rosand, Natalia Rost, Rose Du, Christina Kourkoulis, Thomas Battey, Steven Lubitz, Bertram Mueller-Myhsok, James Meschia, Thomas Brott, Guillaume Pare, Alexander Pichler, Christian Enzinger, Helena Schmidt, Reinhold Schmidt, Stephan Seiler, Susan Blanton, Yoshiji Yamada, Anna Bersano, Tatjana Rundek, Ralph Sacco, Yu-Feng Yvonne Chan, Andreas Gschwendtner, Zhen Deng, Taura Barr, Katrina Gwinn, Roderick Corriveau, Andrew Singleton, Salina Waddy, Lenore Launer, Christopher Chen, Kim En Le, Wei Ling Lee, Eng King Tan, Akintomi Olugbodi, Peter Rothwell, Sabrina Schilling, Vincent Mok, Elena Lebedeva, Christina Jern, Katarina Jood, Sandra Olsson, Helen Kim, Chaeyoung Lee, Laura Kilarski, Hugh Markus, Jennifer Peycke, Steve Bevan, Wayne Sheu, Hung Yi Chiou, Joseph Chern, Elias Giraldo, Muhammad Taqi, Vivek Jain, Olivia Lam, George Howard, Daniel Woo, Steven Kittner, Braxton Mitchell, John Cole, Jeff O'Connell, Dianna Milewicz, Kachikwu Illoh, Bradford Worrall, Colin Stine, Bartosz Karaszewski, David Werring, Reecha Sofat, June Smalley, Arne Lindgren, Bjorn Hansen, Bo Norrving, Gustav Smith, Juan José Martín, Vincent Thijs, Karin Klijn, Femke van't Hof, Ale Algra, Mary Macleod, Rodney Perry, Donna Arnett, Alessandro Pezzini, Alessandro Padovani, Steve Cramer, Mark Fisher, Danish Saleheen, Joseph Broderick, Brett Kissela, Alex Doney, Cathie Sudlow, Kristiina Rannikmae, Scott Silliman, Caitrin McDonough, Matthew Walters, Annie Pedersen, Kazuma Nakagawa, Christy Chang, Mark Dobbins, Patrick McArdle, Yu-Ching Chang, Robert Brown, Devin Brown, Elizabeth Holliday, Raj Kalaria, Jane Maguire, John Attia, Martin Farrall, Anne-Katrin Giese, Myriam Fornage, Jennifer Majersik, Mary Cushman, Keith Keene, Siiri Bennett, David Tirschwell, Bruce Psaty, Alex Reiner, Will Longstreth, David Spence, Joan Montaner, Israel Fernandez-Cadenas, Carl Langefeld, Cheryl Bushnell, Laura Heitsch, Jin-Moo Lee, Kevin Sheth
Language: English
Subfield: Neurology
Field: Medicine
Domain: Health Sciences
Open Access status: hybrid
Estimated APC paid: $4,058
Funders: American Heart Association, Massachusetts General Hospital, South London and Maudsley NHS Foundation Trust, Wellcome Trust, NIHR Biomedical Research Centre, Royal Marsden NHS Foundation Trust/Institute of Cancer Research, National Institute for Health and Care Research, University of Cambridge, Cambridge University Hospitals, Fonds Wetenschappelijk Onderzoek, Ministero della Salute, Vlaamse regering, Stiftung zur Erforschung der Vaskulären Demenz, National Institutes of Health, Medical Research Council, National Health and Medical Research Council, Japan Society for the Promotion of Science, National Institute on Aging, National Institute of Neurological Disorders and Stroke, National Center for Advancing Translational Sciences
Awards: G1194337659, UC Davis Alzheimer's Disease Core Center, G1353455142, G1564468190, NIHR Senior Investigator Award, G232440474, G2388603646, G36433118, Improving prevention of stroke by better understanding of existing risk factors and treatments., G5067462658, Genetic Architecture of Acute Human Brain Ischemia, Development of the personalized prevention system by longitudinal exome-wide association studies of common complex diseases, NIHR Senior Investigator Award, Centre for prevention of stroke and dementia.
OpenAlex ID: W2188742158