Contribution of Common Genetic Variants to Risk of Early-Onset Ischemic Stroke
Thomas Jaworek, Huichun Xu, Brady Gaynor, John W. Cole, Kristiina Rannikmäe, Tara M. Stanne, Liisa Tomppo, Vida Abedi, Philippe Amouyel, Nicole D. Armstrong, John Attia, Steven Bell, Oscar Benavente, Giorgio B. Boncoraglio, Adam S. Butterworth, Jara Cárcel‐Márquez, Zhengming Chen, Michael Chong, Carlos Cruchaga, Mary Cushman, John Danesh, Stéphanie Debette, David Duggan, Jon Peter Durda, Gunnar Engström, Chris Enzinger, Jessica D. Faul, Natalie Fecteau, Israel Fernández‐Cadenas, Christian Gieger, Anne‐Katrin Giese, Raji P. Grewal, Ulrike Grittner, Aki S. Havulinna, Laura Heitsch, Marc C. Hochberg, Elizabeth Holliday, Jie Hu, Andreea Ilinca, Marguerite R. Irvin, Rebecca D. Jackson, Mina A. Jacob, Raquel Rabionet, Jordi Jiménez-Conde, Julie A. Johnson, Yoichiro Kamatani, Sharon L. R. Kardia, Masaru Koido, Michiaki Kubo, Leslie A. Lange, Jin‐Moo Lee, Robin Lemmens, Christopher Levi, Jiang Li, Liming Li, Kuang Lin, Haley Lopez, Sothear Luke, Jane Maguire, Patrick F. McArdle, Caitrin W. McDonough, James F. Meschia, Tiina M. Metso, Martina Müller‐Nurasyid, Timothy D. O’Connor, Martin O’Donnell, Leema Reddy Peddareddygari, Joanna Pera, James A. Perry, Annette Peters, Jukka Putaala, Debashree Ray, Kathryn M. Rexrode, Marta Ribasés, Jonathan Rosand, Peter M. Rothwell, Tatjana Rundek, Kathleen A. Ryan, Ralph L. Sacco, Veikko Salomaa, Cristina Sánchez‐Mora, Reinhold Schmidt, Pankaj Sharma, Agnieszka Słowik, Jennifer A. Smith, Nicholas L. Smith, Sylvia Wassertheil‐Smoller, Martin Söderholm, O. Colin Stine, Daniel Strbian, Cathie Sudlow, Turgut Tatlisumak, Chikashi Terao, Vincent Thijs, Nuria P. Torres‐Aguila, David‐Alexandre Trégouët, Anil M. Tuladhar, Jan H. Veldink, Robin Walters, David R. Weir
Abstract
BACKGROUND AND OBJECTIVES: Current genome-wide association studies of ischemic stroke have focused primarily on late-onset disease. As a complement to these studies, we sought to identify the contribution of common genetic variants to risk of early-onset ischemic stroke. METHODS: We performed a meta-analysis of genome-wide association studies of early-onset stroke (EOS), ages 18-59 years, using individual-level data or summary statistics in 16,730 cases and 599,237 nonstroke controls obtained across 48 different studies. We further compared effect sizes at associated loci between EOS and late-onset stroke (LOS) and compared polygenic risk scores (PRS) for venous thromboembolism (VTE) between EOS and LOS. RESULTS: = 0.008). DISCUSSION: locus, genetically predicted blood group A, and higher genetic propensity for venous thrombosis are more strongly associated with EOS than with LOS, supporting a stronger role of prothrombotic factors in EOS.