| Title | Contribution of Common Genetic Variants to Risk of Early-Onset Ischemic Stroke |
| Authors | Jaworek, Thomas Xu, Huichun Gaynor, Brady J. Cole, John W. Rannikmae, Kristiina Stanne, Tara M. Tomppo, Liisa Abedi, Vida Amouyel, Philippe Armstrong, Nicole D. Attia, John Bell, Steven Benavente, Oscar R. Boncoraglio, Giorgio B. Butterworth, Adam Carcel-Marquez, Jara Chen, Zhengming Chong, Michael Cruchaga, Carlos Cushman, Mary Danesh, John Debette, Stephanie Duggan, David J. Durda, Jon Peter Engstrom, Gunnar Enzinger, Chris Faul, Jessica D. Fecteau, Natalie S. Fernandez-Cadenas, Israel Gieger, Christian Giese, Anne-Katrin Grewal, Raji P. Grittner, Ulrike Havulinna, Aki S. Heitsch, Laura Hochberg, Marc C. Holliday, Elizabeth Hu, Jie Ilinca, Andreea Irvin, Marguerite R. Jackson, Rebecca D. Jacob, Mina A. Rabionet, Raquel Jimenez-Conde, Jordi Johnson, Julie A. Kamatani, Yoichiro Kardia, Sharon L. R. Koido, Masaru Kubo, Michiaki Lange, Leslie Lee, Jin-Moo Lemmens, Robin Levi, Christopher R. Li, Jiang Li, Liming Lin, Kuang Lopez, Haley Luke, Sothear Maguire, Jane McArdle, Patrick F. McDonough, Caitrin W. Meschia, James F. Metso, Tiina Mueller-Nurasyid, Martina O'Connor, Timothy D. O'Donnell, Martin Peddareddygari, Leema R. Pera, Joanna Perry, James A. Peters, Annette Putaala, Jukka Ray, Debashree Rexrode, Kathryn Ribases, Marta Rosand, Jonathan Rothwell, Peter M. Rundek, Tatjana Ryan, Kathleen A. Sacco, Ralph L. Salomaa, Veikko Sanchez-Mora, Cristina Schmidt, Reinhold Sharma, Pankaj Slowik, Agnieszka Smith, Jennifer A. Smith, Nicholas L. Wassertheil-Smoller, Sylvia Soderholm, Martin Stine, O. Colin Strbian, Daniel Sudlow, Cathie L. M. Tatlisumak, Turgut Terao, Chikashi Thijs, Vincent Torres-Aguila, Nuria P. Tregouet, David-Alexandre Tuladhar, Anil M. Veldink, Jan H. Walters, Robin G. Weir, David R. Woo, Daniel Worrall, Bradford B. Hong, Charles C. Ross, Owen A. Zand, Ramin de Leeuw, Frank-Erik Lindgren, Arne G. Pare, Guillaume Anderson, Christopher D. Markus, Hugh S. Jern, Christina Malik, Rainer Dichgans, Martin Mitchell, Braxton D. Kittner, Steven J. |
| Affiliation | Univ Maryland, Sch Med, Div Endocrinol, Baltimore, MD 21201 USA Univ Maryland, Dept Neurol, Diabet & Nutr, Baltimore, MD 21201 USA Univ Maryland, Div Rheumatol & Clin Immunol, Baltimore, MD 21201 USA Univ Maryland, Dept Med, Dept Epidemiol & Publ Hlth, Baltimore, MD 21201 USA Univ Maryland, Inst Genome Sci, Baltimore, MD 21201 USA VA Maryland Hlth Care Syst, Baltimore, MD USA Univ Edinburgh, Usher Inst, Med Informat Ctr, Edinburgh, Midlothian, Scotland Univ Gothenburg, Sahlgrenska Acad, Inst Biomed, Dept Lab Med, Gothenburg, Sweden Helsinki Univ Hosp, Dept Neurol, Helsinki, Finland Univ Helsinki, Helsinki, Finland Geisinger Hlth Syst, Dept Mol & Funct Genom, Danville, PA USA Univ Lille, LabEx DISTALZ, RID AGE Risk Factors & Mol Determinants Aging Rel, U1167, Lille, France Inserm, U1167, Lille, France Ctr Hosp Univ Lille, Lille, France Inst Pasteur, Lille, France Univ Alabama Birmingham, Dept Epidemiol, Birmingham, AL USA Univ Newcastle, Sch Med & Publ Hlth, Callaghan, NSW, Australia Hunter Med Res Inst, Newcastle, NSW, Australia Univ Cambridge, Stroke Res Grp, Cambridge, England Univ Cambridge, Dept Clin Neurosci, British Heart Fdn Cardiovasc Epidemiol Unit, Cambridge, England Univ Cambridge, Dept Publ Hlth & Primary Care, British Heart Fdn Ctr Res Excellence, Cambridge, England Univ Cambridge, Natl Inst Hlth Res, Blood & Transplant Res Unit Donor Hlth & Genom, Cambridge, England Univ Cambridge, Cambridge, England Univ British Columbia, Dept Neurol, Vancouver, BC, Canada Fdn IRCCS Ist Neurol Carlo Besta, Dept Cerebrovasc Dis, Milan, Italy Hlth Data Res UK Cambridge, Cambridge, England Wellcome Genome Campus, Cambridge, England Biomed Res Inst St Pau IIB St Pau, Stroke Pharmacogen & Genet Grp, Barcelona, Spain Univ Oxford, Nuffield Dept Populat Hlth, MRC Populat Hlth Res Unit, Oxford, England Univ Oxford, Nuffield Dept Clin Neurosci, Oxford, England McMaster Univ, DBCVS Res Inst, Dept Pathol & Mol Med, Populat Hlth Res Inst, Hamilton, ON, Canada Thrombosis & Atherosclerosis Res Inst TaARI, Hamilton, ON, Canada Washington Univ, Sch Med, Dept Neurol, St Louis, MO USA Washington Univ, Sch Med, Dept Psychiat, St Louis, MO USA Univ Vermont, Larner Coll Med, Dept Med, Burlington, VT USA Univ Vermont, Larner Coll Med, Lab Clin Biochem Res, Burlington, VT USA Univ Vermont, Larner Coll Med, Dept Med, Burlington, VT USA Wellcome Sanger Inst, Dept Human Genet, Hinxton, England Univ Bordeaux, Inserm Bordeux Populat Hlth Res Ctr, UMR 1219, Bordeaux, France Bordeaux Univ Hosp, Inst Neurodegenerat Dis, Dept Neurol, Bordeaux, France Affiliate City Hope, Translat Genom Res Inst, Quantitat Med & Syst Biol Div, Phoenix, AZ USA Lab Clin Biochem Res, Malmo, Sweden Dept Clin Sci, Malmo, Sweden Lund Univ, Dept Clin Sci, Neurol, Lund, Sweden Med Univ Graz, Dept Neurol, Graz, Austria Univ Michigan, Inst Social Res, Survey Res Ctr, Ann Arbor, MI USA Fundacio Docencia & Recerca MutuaTerrassa, Stroke Pharmacogen & Genet, Terrassa, Spain Helmholtz Zentrum Munchen German Res Ctr Environm, Unit Mol Epidemiol, Neuherberg, Germany Helmholtz Zentrum Munchen German Res Ctr Environm, Inst Epidemiol, Neuherberg, Germany Univ Klinikum Hamburg Eppendorf, Kopf & Neurozentrum, Klin & Poliklin Neurol, Hamburg, Germany St Francis Med Ctr, Neurosci Inst, Trenton, NJ USA Charite Univ Med Ctr, Dept Biostat & Clin Epidemiol, Berlin, Germany Natl Inst Hlth & Welf, Helsinki, Finland Washington Univ, Sch Med, Dept Emergency Med, St Louis, MO USA Washington Univ, Sch Med, Dept Neurol, St Louis, MO USA Harvard Med Sch, Brigham & Womens Hosp, Div Womens Hlth, Boston, MA USA Harvard Med Sch, Brigham & Womens Hosp, Dept Med, Boston, MA USA Harvard Med Sch, Brigham & Womens Hosp, Dept Neurol, Boston, MA USA Harvard TH Chan Sch Publ Hlth, Dept Epidemiol, Boston, MA USA Skane Univ Hosp, Dept Neurol & Rehabil Med, Lund, Sweden Ohio State Univ, Dept Internal Med, Div Endocrinol Diabet & Metab, Columbus, OH USA Ohio State Univ, Ctr Clin & Translat Sci, Columbus, OH USA Radboud Univ Nijmegen Med Ctr, Donders Med Ctr Neurosci, Dept Neurol, Nijmegen, Netherlands Univ Barcelona, Inst Biomed IBUB, Dept Genet Microbiol & Stat, Barcelona, Spain Inst Recerca St Joan de Deu, Esplugas de Llobregat, Spain Univ Autonoma Barcelona, Ctr Invest Biomed Red CIBERER, Barcelona, Spain Univ Autonoma Barcelona, Inst Hosp Mar Invest Med, Dept Neurol, Neurovasc Res Grp, Barcelona, Spain Univ Florida, Coll Pharm, Dept Pharmacotherapy & Translat Res, Gainesville, FL USA Univ Florida, Coll Pharm, Ctr Pharmacogen, Gainesville, FL USA Univ Florida, Coll Med, Div Cardiovasc Med, Gainesville, FL USA Univ Tokyo, Inst Med Sci, Lab Complex Trait Genom, Tokyo, Japan Univ Tokyo, Inst Med Sci, Grad Sch Frontier Sci, Tokyo, Japan Univ Tokyo, Inst Med Sci, Dept Canc Biol, Tokyo, Japan Univ Michigan, Sch Publ Hlth, Dept Epidemiol, Ann Arbor, MI USA RIKEN Ctr Integrat Med Sci, Dept Canc Biol, Yokohama, Kanagawa, Japan RIKEN Ctr Integrat Med Sci, Yokohama, Kanagawa, Japan Univ Colorado Denver, Dept Med, Anschutz Med Campus, Aurora, CO USA KU Leuven Univ Leuven, VIB Ctr Brain & Dis Res, Dept Neurosci, Expt Neurol, Leuven, Belgium Univ Hosp Leuven, Dept Neurol, Leuven, Belgium Hunter Med Res Inst, John Hunter Hosp, Newcastle, NSW, Australia Univ Newcastle, Newcastle, NSW, Australia Univ Newcastle, Prior Res Ctr Stroke & Brain Injury, Newcastle, NSW, Australia Peking Univ, Dept Epidemiol & Biostat, Peking Univ Hlth Sci Ctr, Beijing, Peoples R China Mayo Clin, Dept Neurol, Jacksonville, FL USA Univ Technol Sydney, Sch Nursing & Midwifery, Fac Hlth, Sydney, NSW, Australia Helsinki Univ Cent Hosp, Dept Neurol, Helsinki, Finland German Res Ctr Environm Hlth, Helmholtz Zentrum Munchen, Inst Genet Epidemiol, Neuherberg, Germany Johannes Gutenberg Univ Mainz, Univ Med Ctr, Inst Med Biostat Epidemiol & Informat IMBEI, Mainz, Germany Ludwig Maximilians Univ Munchen, Dept Med 1, Munich, Germany Univ Maryland, Sch Med, Dept Med, Baltimore, MD USA Natl Univ Ireland, Hlth Res Board Clin Res Facil Geata Eolais, Galway, Ireland Jagiellonian Univ, Dept Neurol, Krakow, Poland Ludwig Maximilians Univ Munchen, Inst Med Informat Sci Biometry & Epidemiol, Munich, Germany Johns Hopkins Univ, Bloomberg Sch Publ Hlth, Dept Epidemiol, Baltimore, MD USA Univ Autonoma Barcelona, Vall dHebron Res Inst VHIR, Grp Psychiat Mental Hlth & Addict, Psychiat Genet Unit, Barcelona, Spain Hosp Univ Vall dHebron, Dept Psychiat, Barcelona, Spain Inst Salud Carlos III, Biomed Network Res Ctr Mental Hlth CIBERSAM, Madrid, Spain Univ Barcelona, Fac Biol, Dept Genet Microbiol & Stat, Barcelona, Spain Massachusetts Gen Hosp, McCance Ctr Brain Hlth, Boston, MA USA MGH, Ctr Genom Med, Boston, MA USA MGH, Dept Neurol, Boston, MA USA Broad Inst, Program Med & Populat Genet, Cambridge, MA USA Univ Miami, Miller Sch Med, Dept Neurol, Coral Gables, FL 33124 USA Univ Miami, Miller Sch Med, Evelin F McKnight Brain Inst, Coral Gables, FL 33124 USA Royal Holloway Univ London, Inst Cardiovasc Res, London, England Ashford & St Peters Hosp, Surrey, England Univ Washington, Grp Hlth Cooperat, Grp Hlth Res Inst, Seattle, WA USA Univ Washington, Dept Epidemiol, Seattle, WA USA VA Off Res & Dev, Seattle Epidemiol Res & Informat Ctr, Seattle, WA USA Albert Einstein Coll Med, Dept Epidemiol & Populat Hlth, New York, NY USA Hlth Data Res UK, BHF Data Sci Ctr, London, England Sahlgrens Univ Hosp, Reg Vastra Gotaland, Dept Neurol, Gothenburg, Sweden Sahlgrens Univ Hosp, Reg Vastra Gotaland, Dept Clin Genet & Genom, Gothenburg, Sweden Univ Gothenburg, Sahlgrenska Acad, Inst Neurosci & Physiol, Dept Clin Neurosci, Gothenburg, Sweden Univ Melbourne, Florey Inst Neurosci & Mental Hlth, Stroke Theme, Melbourne, Vic, Australia Austin Hlth, Dept Neurol, Heidelberg, Vic, Australia Univ Utrecht, Univ Med Ctr Utrecht, Brain Ctr, Dept Neurol, Utrecht, Netherlands Univ Cincinnati, Coll Med, Dept Neurol & Rehabil Med, Cincinnati, OH 45221 USA Univ Virginia, Sch Med, Dept Neurol, Charlottesville, VA USA Univ Virginia, Sch Med, Dept Publ Hlth Sci, Charlottesville, VA USA Skane Univ Hosp, Neurol Sect, Lund, Sweden Broad Inst MIT & Harvard, Program Med & Populat Genet, Cambridge, MA USA Ludwig Maximilians Univ Munchen, Univ Hosp, Inst Stroke & Dementia Res ISD, Munich, Germany Munich Cluster Syst Neurol SyNergy, Munich, Germany German Ctr Neurodegenerat Dis DZNE, Munich, Germany Vet Adm Med Ctr, Geriatr Res & Educ Clin Ctr, Baltimore, MD USA |
| Keywords | ABO BLOOD-GROUP GENOME-WIDE ASSOCIATION CARDIOVASCULAR-DISEASE LOCUS GENOTYPE |
| Issue Date | 18-Oct-2022 |
| Publisher | NEUROLOGY |
| 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 We observed genome-wide significant associations of EOS with 2 variants in ABO, a known stroke locus. These variants tag blood subgroups O1 and A1, and the effect sizes of both variants were significantly larger in EOS compared with LOS. The odds ratio (OR) for rs529565, tagging O1, was 0.88 (95% confidence interval [CI]: 0.85-0.91) in EOS vs 0.96 (95% CI: 0.92-1.00) in LOS, and the OR for rs635634, tagging A1, was 1.16 (1.11-1.21) for EOS vs 1.05 (0.99-1.11) in LOS; p-values for interaction = 0.001 and 0.005, respectively. Using PRSs, we observed that greater genetic risk for VTE, another prothrombotic condition, was more strongly associated with EOS compared with LOS (p = 0.008). Discussion The ABO 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. |
| URI | http://hdl.handle.net/20.500.11897/657830 |
| ISSN | 0028-3878 |
| DOI | 10.1212/WNL.0000000000201006 |
| Indexed | SCI(E) |
| Appears in Collections: | 公共卫生学院 |
