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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)
Verlagsversion Forschungsdaten DOI PMC
Open Access Hybrid
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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Publikationstyp Artikel: Journalartikel
Dokumenttyp Wissenschaftlicher Artikel
Sprache englisch
Veröffentlichungsjahr 2022
HGF-Berichtsjahr 2022
ISSN (print) / ISBN 0028-3878
e-ISSN 1526-632X
Zeitschrift Neurology
Quellenangaben Band: 99, Heft: 16, Seiten: E1738-E1754 Artikelnummer: , Supplement: ,
Verlag Lippincott Williams & Wilkins
Begutachtungsstatus Peer reviewed
Institut(e) Institute of Epidemiology (EPI)
Institute of Genetic Epidemiology (IGE)
POF Topic(s) 30202 - Environmental Health
30501 - Systemic Analysis of Genetic and Environmental Factors that Impact Health
Forschungsfeld(er) Genetics and Epidemiology
PSP-Element(e) G-504091-004
G-504100-001
G-504000-010
Förderungen American Heart Association
U.S. Department of Veterans Affairs
National Institutes of Health
DOI 10.1212/WNL.0000000000201006
WOS ID WOS:000876062000022
PubMed ID 36240095
Erfassungsdatum 2022-10-26
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