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Jaworek, T.* ; Xu, H.* ; Gaynor, B.J.* ; Cole, J.W.* ; Rannikmäe, K.* ; Stanne, T.M.* ; Tomppo, L.* ; Abedi, V.* ; Amouyel, P.* ; Armstrong, N.D.* ; Attia, J.* ; Bell, S.* ; Benavente, O.R.* ; Boncoraglio, G.B.* ; Butterworth, A.* ; Cárcel-Márquez, J.* ; Chen, Z.* ; Chong, M.* ; Cruchaga, C.* ; Cushman, M.* ; Danesh, J.* ; Debette, S.* ; Duggan, D.J.* ; Durda, J.P.* ; Engström, G.* ; Enzinger, C.* ; Faul, J.D.* ; Fecteau, N.S.* ; Fernandez-Cadenas, I.* ; Gieger, C. ; Giese, A.K.* ; Grewal, R.P.* ; Grittner, U.* ; Havulinna, A.S.* ; Heitsch, L.* ; Hochberg, M.C.* ; Holliday, E.* ; Hu, J.* ; Ilinca, A.* ; Irvin, M.R.* ; Jackson, R.D.* ; Jacob, M.A.* ; Janssen, R.R.* ; Jimenez-Conde, J.* ; Johnson, J.A.* ; Kamatani, Y.* ; Kardia, S.L.* ; Koido, M.* ; Kubo, M.* ; Lange, L.* ; Lee, J.M.* ; Lemmens, R.* ; Levi, C.R.* ; Li, J.* ; Li, L.* ; Lin, K.* ; Lopez, H.* ; Luke, S.* ; Maguire, J.* ; McArdle, P.F.* ; McDonough, C.W.* ; Meschia, J.F.* ; Metso, T.M.* ; Müller-Nurasyid, M. ; O'Connor, T.D.* ; O'Donnell, M.* ; Peddareddygari, L.R.* ; Pera, J.* ; Perry, J.A.* ; Peters, A. ; Putaala, J.* ; Ray, D.W.* ; Rexrode, K.* ; Ribasés, M.* ; Rosand, J.* ; Rothwell, P.M.* ; Rundek, T.* ; Ryan, K.A.* ; Sacco, R.L.* ; Salomaa, V.* ; Sánchez-Mora, C.* ; Schmidt, R.* ; Sharma, P.* ; Slowik, A.* ; Smith, J.A.* ; Smith, N.L.* ; Wassertheil-Smoller, S.* ; Soederholm, M.* ; Stine, O.C.* ; Strbian, D.* ; Sudlow, C.L.* ; Tatlisumak, T.* ; Terao, C.* ; Thijs, V.* ; Torres-Aguila, N.P.* ; Tregouet, D.A.* ; Tuladhar, A.M.* ; Veldink, J.H.* ; Walters, R.G.* ; Weir, D.R.* ; Woo, D.* ; Worrall, B.B.* ; Hong, C.C.* ; Ross, O.A.* ; Zand, R.* ; Leeuw, F.E.* ; Lindgren, A.G.* ; Paré, G.* ; Anderson, C.D.* ; Markus, H.S.* ; Jern, C.* ; Malik, R.* ; Dichgans, M.* ; Mitchell, B.D.* ; Kittner, S.J.*

Contribution of common genetic variants to risk of early onset ischemic stroke.

Neurology 99, E1738-E1754 (2022)
Publ. Version/Full Text Research data DOI PMC
Open Access Gold (Paid Option)
Creative Commons Lizenzvertrag
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 identifythe 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, using individual level data or summary statistics in 16,730 cases and 599,237 non-stroke 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 for venous thromboembolism between EOS and LOS. RESULTS: We observed genome-wide significant associations of EOS with two 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 to LOS. The odds ratio (OR) for rs529565, tagging O1, 0.88 (95% 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 polygenic risk scores, we observed that greater genetic risk for venous thromboembolism, another prothrombotic condition, was more strongly associated with EOS compared to 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.
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Publication type Article: Journal article
Document type Scientific Article
Corresponding Author
ISSN (print) / ISBN 0028-3878
e-ISSN 1526-632X
Journal Neurology
Quellenangaben Volume: 99, Issue: 16, Pages: E1738-E1754 Article Number: , Supplement: ,
Publisher Lippincott Williams & Wilkins
Non-patent literature Publications
Reviewing status Peer reviewed
Institute(s) Institute of Epidemiology II (EPI2)
Institute of Genetic Epidemiology (IGE)
Grants American Heart Association
U.S. Department of Veterans Affairs
National Institutes of Health